The Functions of the Amyloid Precursor Protein Gene and Its Derivative Peptides: II Experimental Evidence and Clinical Studies — Oak Academic Publishing
Research ArticleOpen AccessGoogle Scholar indexed
The Functions of the Amyloid Precursor Protein Gene and Its Derivative Peptides: II Experimental Evidence and Clinical Studies
In vitro studies suggest Amyloid Precursor Protein Gene (APP) is involved in interaction with the extracellular matrix, neurite growth, adhesion, development, synaptic function, platelet function, and interaction with GTP binding proteins. In vivo experiments show a role in embryonic development, response to cerebral excitotoxicity and gliosis, response to brain injury including ischaemia, hypothalamic function, locomotor function, learning and memory. In vitro observations indicate Aβ has a role in amyloid formation, excitotoxic neuronal injury, tachykinin interaction, endothelial vasoconstrictor response, calcium and oxidative stress, free radical interaction, cell membrane fluidity, apoptosis, astrocyte stimulation, and microglial interaction. Other studies suggest important roles for Aβ oligomers in synaptic function and as an antimicrobial peptide. In vivo investigations show involvement in memory function, the blood brain barrier, and tachykinin response to cerebral injury.
KeywordsAmyloid Precursor Protein Gene
Z. Zhong, J. Higaki, K. Wang, R. Catalano, D. Quon and B. Cordell, “Secretion of β-Amyloid Precursor Protein Involves Multiple Cleavage Sites,” Journal of Biological Chemistry, Vol. 269, No. 1, 1994, pp. 627-632.
S. B. Roberts, J. A. Ripellino, K. M. Ingalls, N. K. Robakis and K. M. Felstein, “Non-Amyloidogenic Cleavage of the B-Amyloid Precursor Protein by an Integral Membrane Metalloendopeptidase,” Journal of Biological Chemistry, Vol. 269, No. 4, 1994, pp. 3111- 3116.
M. R. Palmert, M. B. Podlisny, D. S. Witker, T. Oltersdorf, L. H. Younkin, D. J. Selkoe and S. G. Younkin, “The B-Amyloid Protein Precursor of Alzheimer Disease Has Soluble Derivatives Found in Human Brain and Cere- brospinal Fluid,” Proceedings of the National Acadamy of Sciences of the United States of America, Vol. 86, 1989, pp. 6338-6342.
P. Seubert, C. Vigo-Pelfrey, F. Esch, M. Lee, H. Dovey, D. Davis, S. Sinha, M. Schlossmacher, J. Whaley and C. Swindlehurst, “Isolation and Quantification of Soluble Alzheimer’s B-Peptide from Biological Fluids,” Nature, Vol. 359, No. 6393, 1992, pp. 325-327.
F. S. Esch, P. S. Keim, E. C. Beattie, R. W. Blacher, A. R. Culwell, T. Oltersdorf, D. McClure and P. J. Ward, “Cleavage of Amyloid B-Peptide during Constitutive Pro- cessing of Its Precursor,” Science, Vol. 248, 1990, pp. 1122-1124.
C. Haass, E. H. Koo, A. Mellon, A. Y. Hung and D. J. Selkoe, “Targeting of Cell-Surface B-Amyloid Precursor Protein to Lysosomes: Alternative Processing into Amyloid-Bearing Fragments,” Nature, Vol. 357, No. 6378, 1992, pp. 500-502.
C. Haass, M. G. Schlossmacher, A. Y. Hung, C. Vigo- Pelfrey, A. Mellon, B. L. Ostaszewski, I. Lieberburg, E. H. Koo, D. Schenk and D. B. Teplow, “Amyloid B- Peptide is Produced by Cultured Cells During Normal Metabolism,” Nature, Vol. 359, 1992, pp. 322-325.
P. Seubert, T. Oltersdorf, M. G. Lee, R. Barbour, C. Blomquist, D. L. Davis, K. Bryant, L. C. Fritz, D. Galasko and L. J. Thal, “Secretion of β-Amyloid Precursor Protein Cleaved at the Aminoterminus of the β- Amyloid Pep- tide,” Nature, Vol. 361, 1993, pp. 260-263.
C. Haass and D. J. Selkoe, “Cellular Processing of β- Amyloid Precursor and the Genesis of Amyloid B- Peptide,” Cell, Vol. 75, No. 6, 1993, pp. 1039-1042.
M. L. Oster-Granite, D. L. McPhie, J. Greenan and R. L. Neve, “Age-Dependent Neuronal and Synaptic Degenera- tion in Mice Transgenic for the C Terminus of the Amyloid Precursor Protein,” Journal of Neuroscience, Vol. 16, No. 21, 1996, pp. 6732-6741.
M. N. Pangalos, J. Shioi, S. Efthimiopoulos, A. Wu and N. K. Robakis, “Characterization of Appican, the Chondroitin Sulfate Proteoglycan form of the Alzheimer Amyloid Pre- cursor Protein,” Neurodegeneration, Vol. 5, No. 4, 1996, pp. 445-451.
B. Allinquant, K. L. Moya, C. Bouillot and A. Prochiantz, “Amyloid Precursor Protein in Cortical Neurons: Existence of Two Pools Differentially Distributed in Axons and Dendrites and Association with Cytoskeleton,” Journal of Neuroscience, Vol. 14, 1994, pp. 6842-6854.
Y. H. Suh, Y. H. Chong, S. H. Kim, W. Choi, K. Min, S. J. Jeong, S. P. Fraser and M. B. Djamgoz, “Molecular Physiology, Biochemistry and Pharmacology of Alzhei- mer’s Amyloid Precursor Protein (APP),” Annals of the New York Acadamy of Sciences, Vol. 786, 1996, pp. 169- 183.
D. Schubert, L. W. Jin, T. Saitoh and G. Cole, “The Regulation of Amyloid B Protein Precursor Secretion and its Modulatory Role in Cell Adhesion,” Neuron, Vol. 3, 1989, pp. 689-694.
C. J. Smith, D. Widon and P. Brachet, “Nerve Growth Factor-Induced Neuronal Differentiation is Accompanied by Differential Splicing of B-Amyloid Precursor mRNAs in the PC12 Cell Line,” Molecular Brain Research, Vol. 10, 1991, pp. 351-354.
E. A. Milward, R. Papadopoulos, S. J. Fuller, R. D. Moir, D. Small, K. Beyreuther and C. L. Masters, “The Amyloid Protein Precursor of Alzheimer's Disease is a Mediator of the Effects of Nerve Growth Factor on Neurite Outgrowth,” Neuron, Vol. 9, No. 1, 1992, pp. 129-137.
J. J. Luo, W. Wallace, T. Riccioni, D. K. Ingram, G. S. Roth and J. W. Kusiak, “Death of PC12 Cells and Hippocampal Neurons Induced by Adenoviral-Mediated FAC Human Amyloid Precursor Protein Gene Expres- sion,” Journal of Neuroscience Research, Vol. 55, 1999, pp. 629-642.
H. J. Clarris, V. Nurcombe, D. H. Small, K. Beyreuther and C. L. Masters, “Secretion of Nerve Growth Factor From Septum Stimulates Neurite Outgrowth and Release of the Amyloid Protein Precursor of Alzheimer’s Disease From Hippocampal Explants,” Journal of Neuroscience Research, Vol. 38, No. 3, 1994, pp. 248-258.
S. Rossner, U. Ueberham, R. Schliebs, J. R. Perez-Polo and V. Bigl, “Neurotrophin Building to the p75 Neurotro- phin Receptor is Necessary but not Sufficient to Mediate NGF-Effects on APP Secretion in PC-12 Cells,” Journal of Neural Transmission, Vol. 54 Suppl, 1998, pp. 279- 285.
K. Yoshikawa, T. Aizawa and Y. Hayashi, “Degeneration In Vitro of Post-Mitotic Neurons Over Expressing the Alzheimer Amyloid Protein Precursor,” Nature, Vol. 359, 1992, pp. 64-67.
N. Y. Barnes, L. Li, K. Yoshikawa, L. M. Schwartz, R. W. Oppenheim and C. E. Milligan, “Increased Production of Amyloid Precursor Protein Provides a Substrate for Caspase-3 in Dying Motoneurons,” Journal of Neurosci- ence, Vol. 18, No. 15, 1998, pp. 5869-5880.
D. Schubert and C. Behl, “The Expression of Beta Amy- loid Protein Precursor Protects Nerve Cells From B-Amy- loid and Glutamate Toxicity and Alters Their Interaction with the Extracellular Matrix,” Brain Research, Vol. 629, No. 2, 1993, pp. 275-282. doi:10.1016/0006-8993(93)91331-L
D. H. Small, V. Nurcombe, G. Reed, H. Clarris, R. Moir, K. Beyreuther and C. L. Masters, “A Heparin-Binding Domain in the Amyloid Protein Precursor of Alzheimer's Disease is Involved in the Regulation of Neurite Out- growth,” Journal of Neuroscience, Vol. 14, No. 4, 1994, pp. 2117-2127.
W. Q. Qiu, A. Ferreira, C. Miller, E. H. Koo and D. J. Selkoe, “Cell-Surface B-Amyloid Precursor Protein Sti- mulates Neurite Outgrowth of Hippocampal Neurons in an Isoform-Dependent Manner,” Journal of Neuroscience, Vol. 15, 1995, pp. 2157-2167.
L. W. Jin, H. Ninomiya, J. M. Rocn, D. Schubert, E. Maslian, D. A. Otero and T. Saitoh, “Peptides Containing the RERMS Sequence of Amyloid β/A4 Protein Precursor Bind Cell Surface and Promote Neurite Extension,” Journal of Neuroscience, Vol. 14, 1994, pp. 5461-5470.
F. G. Klier, G. Cole, W. Stallcup and D. Schubert, “Amy- loid B-Protein Precursor is Associated with Extracellular Matrix,” Brain Research, Vol. 515, 1990, pp. 336-342.
J. Hoffmann, C. U. Pietrzik, M. P. Kummer, C. Twiesselmann, C. Bauer and V. Herzog, “Binding and Selective Detection of the Secretory N-Terminal Domain of the Alzheimer Amyloid Precursor Protein on Cell Surfaces,” Journal of Histochemistry and Cytochemistry, Vol. 47, No. 3, 1999, pp. 373-382.
K. Barber, S. A. Enam, S. Bodovitz, M. Falduto, D. Frail and W. L. Klein, “Particulate Forms of APP in the Extracellular Milieu of Cultured Cells,” Experimental Neurology, Vol. 132, No. 1, 1995, pp. 42-53.
S. Narindrasorasak, D. Lowery, P. Gonzalez-deWhitt, R. A. Poorman, B. Greenberg and R. Kisilevsky, “High Affinity Interactions Between the Alzheimer’s B- Amy- loid Precursor Proteins and the Basement Membrane form of Heparin Sulfate Proteoglycan,” Journal of Biological Chemistry, Vol. 266, No. 20, 1991, pp. 12878-12883.
K. C. Breen, “APP-Collagen Interaction is Mediated by a Heparin Bridge Mechanism,” Molecular and Chemical Neuropathology, Vol. 16, No. 1-2, 1992, pp. 109-121.
M. C. Kibbey, M. Jucker, B. S. Weeks, R. L. Neve, W. E. Van Nostrand and H. K. Kleinman, “β-Amyloid Precursor Protein Binds to the Neurite-Promoting IKVAV Site of Laminin,” Proceedings of the National Acadamy of Sciences of the United States of America, Vol. 90, No. 2, 1993, pp. 10150-10153.
L. Buee, W. Ding, J. P. Anderson and S. Narindrasorasak, “Binding of Vascular Heparan Sulfate Proteoglycan to Alzheimer’s Amyloid Precursor Protein Is Mediated in part by the N-terminal Region of A4 Peptide,” Brain Research, Vol. 627, No. 2, 1993, pp. 199-204.
L. Buee, W. Ding, A. Delacourte and H. Fillit, “Binding of Secreted Human Neuroblastoma Proteoglycans to the Alzheimer’s Amyloid A4 Peptide,” Brain Research, Vol. 601, No. 1-2, 1993, pp. 154-163. doi:10.1016/0006-8993(93)91706-X
H. Ninomiya, J. M. Roch, L. W. Jin and T. Saitoh, “Secreted Form of Amyloid Beta/A4 Protein Precursor (APP) Binds to Two Distinct APP Binding Sites on Rat B103 Neuron-Like Cells through Two Different Domains, But Only One Site is Involved in Neuritotropic Activity,” Journal of Neurochemistry, Vol. 63, No. 2, 1994, pp. 495-500.
U. Monning, R. Sandbrink, A. Weidemann, R. B. Banati, C. L. Masters and K. Beyreuther, “Extracellular Matrix Influences the Biogenesis of Amyloid Precursor Protein in Microglial Cells,” Journal of Biological Chemistry, Vol. 270, No. 13, 1995, pp. 7104-7110. doi:10.1074/jbc.270.13.7104
G. Multhaup, H. Mechler and C. L. Masters, “Cha- racterization of the High Affinity Heparin Binding Site of the Alzheimer’s Disease Beta A4 Amyloid Precursor Protein (APP) and its Enhancement by Zinc (II),” Journal of Molecular Recognition, Vol. 8, No. 4, 1995, pp. 247- 257.
S. S. Mok, G. Sberna, D. Heffernan, R. Cappai, D. Galatis, H. J. Clarris, W. H. Sawyer, K. Beyreuther, C. L. Masters and D. H. Small, “Expression and Analysis of Heparin-Binding Regions of the Amyloid Precursor Protein of Alzheimer’s Disease,” FEBS Letters, Vol. 415, No. 3, 1997, pp. 303-307.
H. J. Clarris, R. Cappai, D. Heffernan, K. Beyreuther, C. L. Masters and D. H. Small, “Idenification of Heparin- Binding Domains in the Amyloid Precursor Protein of Alzheimer’s Disease by Deletion Mutagenesis and Peptide Mapping,” Journal of Neurochemistry, Vol. 68, No. 3, 1997, pp. 1164-1172.
T. Yamazaki, E. H. Koo and D. J. Selkoe, “Cell Surface Amyloid Beta-Protein Precursor Colocalizes with Beta 1 Integrins at Substrate Contact Sites in Neural Cells,” Journal of Neuroscience, Vol. 17, No. 3,1997, pp. 1004- 1010.
S. Fisher, J. D. Gearhart and M. L. Oster-Granite, “Expression of the Amyloid Precursor Protein Gene in Mouse Oocytes and Embryos,” Proceedings of the National Acadamy of Sciences of the United States of America, Vol. 88, No. 5, 1991, pp. 1779-1782.
A. Y. Hung, E. H. Koo, C. Haass and D. J. Selkoe, “Increased Expression of B-Amyloid Precursor Protein During Neuronal Differentiation is not Accompanied by Secretory Cleavage,” Proceedings of the National Acadamy of Sciences of the United States of America, Vol. 89, 1992, pp. 9439-9443.
K. Yoshikawa, T. Aizawa and K. Maruyama, “Neural Differentiation Increases Expression of Alzheimer Amyloid Protein Precursor in Murine Embryonal Carcinoma Cells,” Biochemical and Biophysical Research Communications, Vol. 171, 1990, pp. 204-209.
W. Schubert, R. Prior, A. Weidmann, H. Dirksen, G. Multhaup, C. L. Masters and K. Beyreuther, “Lo- calization of Alzheimer BA4 Amyloid Precursor Protein at Central and Peripheral Sites,” Brain Research, Vol. 563, 1991, pp. 184-194.
K. Fukuchi, K. Kamino, S. S. Deeb, A. C. Smith, T. Dang and G. M. Martin, “Overexpression of Amyloid Precursor Protein Alters its Normal Processing and is Associated With Neurotoxicity,” Biochemical and Biophysical Research Communications, Vol. 182, No. 1, 1992, pp. 165-173. doi:10.1016/S0006-291X(05)80126-3
T. Morimoto, I. Ohsawa, C. Takamura, M. Ishiguro, Y. Nakamura and S. Kohsake, “Novel Domain-Specific Actions of Amyloid Precursor Protein on Developing Synapses,” Journal of Neuroscience, Vol. 18, No. 22, 1998, pp. 9386-9393.
M. Usami, W. Yamao-Harigaya and K. Maruyama, “The Triplet of Lysine Residues (Lys 724-Lys725-Lys726) of Alzheimer’s Amyloid Precursor Protein Plays an Important Role in Membrane Anchorage and Processing,” Journal of Neurochemistry, Vol. 61, No. 1,1993, pp. 239-246. doi:10.1111/j.1471-4159.1993.tb03560.x
E. H. Koo, S. S. Sisodia, D. R. Archer, L. J. Martin, A. Weidemann, K. Beyreuther, P. Fischer, C. L. Masters and D. L. Price, “Precursor of Amyloid Protein in Alzheimer Disease Undergoes Fast Anterograde Axonal Transport,” Proceedings of the National Acadamy of Sciences of the United States of America, Vol. 87, No. 4, 1990, pp. 1561-1565.
J. G. Calvenor, A. Friedhuber, S. J. Fuller, K. Beyreuther and C. L. Masters, “Expression of the Amyloid Precursor Protein of Alzheimer’s Disease on the Surface of Transfected HeLa Cells,” Experimental Cell Research, Vol. 220, No. 2, 1995, pp. 474-481.
A. I. Bush, R. N. Martins, B. Rumble, R. Moir, S. Fuller, E. Milward, J. Currie, D. Ames, A. Weidemann and P. Fischer, “The Amyloid Precursor Protein of Alzheimer’s Disease is Released by Human Platelets,” Journal of Biological Chemistry, Vol. 265, No. 26, 1990, pp. 15977- 15983.
R. P. Smith, D. A. Higuchi and G. J. Broze, “Platelet Coagulation Factor XIa-Inhibitor, a Form of Alzheimer Amyloid Precursor Protein,” Science, Vol. 248, No. 4959, 1990, pp. 1126-1128.
M. J. Bullido, M. A. Munoz-Fernandez, M. Recuero, M. Fresno and F. Valdivieso, “Alzheimer’s Amyloid Precur- sor Protein is Expressed on the Surface of Hematopoietic Cells upon Activation,” Biochimica et Biophysica Acta, Vol. 1313, No. 1, 1996, pp. 54-62. doi:10.1016/0167-4889(96)00015-8
N. Jahroudi, J. Kitney, J. S. Greenberger and R. Bowser, “Endothelial Cell Dysfunction in Response to Intracellu- lar Overexpression of Amyloid Precursor Protein,” Journal of Neuroscience Research, Vol. 54, No. 6, 1998, pp. 828-839.
J. R. Ciallella, V. V. Rangnekar and J. McGillis, “Heat Shock Alters Alzheimer’s Beta Amyloid Precursor Protein Expression in Human Endothelial Cells,” Journal of Neuroscience Research, Vol. 37, No. 6, 1994, pp. 769- 776.
T. A. Davies, A. M. Billingslea, H. J. Long, H. Tibbles, J. M. Wells, P. B. Eisenhauer, S. J. Smith, D. H. Cribbs, R. E. Fine and E. R. Simons, “Brain Endothelial Cell Enzymes Cleave Platelet-Retained Amyloid Precursor Protein,” Journal of Laboratory and Clinical Medicine, Vol. 132, No. 4, 1998, pp. 341-350.
S. Gloor, K. Odink, J. Guenther, H. Nick and D. Monard, “A Glia-Derived Neurite Promoting Factor With Protease Inhibitory Activity Belongs to the Protease Nexins,” Cell, Vol. 47, No. 5, 1986, pp. 687-693.
J. Guenther, H. Nick and D. Monard, “A Glial-Derived Neurite-Promoting Factor with Protease Inhibitory Activity,” EMBO Journal, Vol. 4, No. 8, 1985, pp. 1963- 1966.
H. Tanahashi and T. Tabira, “X11L2, a New Member of the X11 Protein Family, Interacts with Alzheimer’s Beta-Amyloid Precursor Protein,” Biochemical and Bio- physical Research Communications, Vol. 255, No. 3, 1999, pp. 663-667.
D. Monard, E. Niday, A. Limat and F. Solomon, “Inhibition of Protease Activity Can Lead to Neurite Extension in Neuroblastoma Cells,” Progress in Brain Research, Vol. 58, 1983, pp. 359-365.
T. B. Shea, “Role of Glial-Derived Nexin in Neuronal Differentiation and in Acute Brain Injury and Potential Involvement in Exacerbation of Neurodegeneration in Alzheimer’s Disease,” Brain Research Reviews, Vol. 20, No. 2, 1995, pp. 171-184.
R. Joseph, W. Tsang, E. Han and G. M. Saed, “Neuronal B-Amyloid Precursor Protein Gene Expression: Regula- tion by Aurintricarboxylic Acid,” Brain Research, Vol. 625, 1993, pp. 244-255. doi:10.1016/0006-8993(93)91065-Z
C. J. Smith, E. M. Johnson, P. Osborn, R. S. Freman, I. Neveu and P. Brachet, “NGF Deprivation and Neuronal Degeneration Trigger Altered β-Amyloid Precursor Proetin Expression in the Rat Superior Cervical Ganglion in Vivo and in Vitro,” Molecular Brain Research, Vol. 17, No. 3-4, 1993, pp. 328-354.
K. Abe, P. H. St George-Hyslop, R. E. Tanzi and K. Kogure, “Induction of Amyloid Precursor Protein mRNA After Heat Shock in Cultured Human Lymphoblastoid Cells,” Neuroscience Letters, Vol. 125, No. 2, 1991, pp. 169-171.
J. D. Buxbaum, M. Oishi, H. I. Chen, R. Pinkas- Kramarski, E. A. Jaffe, S. E. Gandy and P. Greengard, “Cholinergic Agonists and Interleukin-1 Regulate Processing and Secretion of the Alzheimer B/A4 Amyloid Protein Precursor,” Proceedings of the National Acadamy of Sciences of the United States of America, Vol. 89, 1992, pp. 10075-10078.
G. Forloni, F. Demicheli, S. Giorgi, C. Bendotti and N. Angeretti, “Expression of Amyloid Precursor Protein mRNAs in Endothelial, Neuronal and Glial Cells: Modulation by Interleukin-1,” Molecular Brain Research, Vol. 16, No. 1-2, 1992, pp. 128-134.
C. W. Gray and A. J. Patel, “Regulation of B-Amyloid Precursor Protein Isoform mRNAs by Transforming Growth Factor-B1 and Interleukin-1B in Astrocytes,” Molecular Brain Research, Vol. 19, 1993, pp. 251-256.
U. Monning, R. Sandbrink, R. B. Banati, C. L. Masters and K. Beyreuther, “Transforming Growth Factor Beta Mediates Increase of Mature Transmembrane Amyloid Precursor Protein in Microglial Cells,” FEBS Letters, Vol. 342, No. 3, 1994, pp. 267-272.
F. Yang, L. Jansen, W. E. Friedrichs, J. M. Buchanan and B. H. Bowman, “IL-1B Decreases Expression of Amyloid Precursor Protein Gene in Human Glioma Cells,” Biochemical and Biophysical Research Communications, Vol. 191, 1993, pp. 1014-1019.
J. P. Vasilakos, R. T. Carroll, M. R. Emmerling, P. D. Doyle, R. E. Davis, K. S. Kim and B. D. Shivers, “Interleukin-1 Beta Dissociates Beta-Amyloid Precursor Protein and Beta-Amyloid Peptide Secretion,” FEBS Letters, Vol. 354, No. 3, 1994, pp. 289-292.
R. Del Bo, N. Angeretti, E. Lucca, M. G. De Simoni and G. Forloni, “Reciprocal Control of Inflammatory Cytokines, IL-1 and IL-6, and B-Amyloid Production in Cultures,” Neuroscience Letters, Vol. 188, No. 1, 1995, pp. 70-74.
J. T. Rogers, L. M. Leiter, J. McPhee, C. M. Cahill, S. S. Zhan, H. Potter and L. N. Nilsson, “Translation of the Alzheimer Amyloid Precursor Protein mRNA is Up- Regulated by Interleukin-1 Through 5’ Untranslated Region Sequences,” Journal of Biological Chemistry, Vol. 274, No. 10, 1999, pp. 6421-6431.
I. Nishimoto, T. Okamoto, Y. Matsuura, S. Takahashi, T. Okamoto, Y. Murayama and E. Ogata, “Alzheimer Amyloid Protein Precursor Complexes with Brain GTP- Binding Protein G,” Nature, Vol. 362, No. 6415, 1993, pp. 75-79.
H. Schulze, A. Schuler, D. Stuber, H. Dobeli, H. Langen and G. Huber, “Rat Brain Glyceraldehyde-3-Phosphate Dehydrogenase Interacts with the Recombinant Cyto- plasmic Domain of Alzheimer’s Beta-Amyloid Precursor Protein,” Journal of Neurochemistry, Vol. 60, No. 5, 1993, pp. 1915-22.
S. W. Barger and M. P. Mattson, “Isoform-Specific Modulation by Apolipoprotein E of the Activities of Secreted Beta-Amyloid Precursor Protein,” Journal of Neurochemistry, Vol. 69, No. 1, 1997, pp. 60-67.
S. Hass, F. Fresser, S. Kochl, K. Beyreuther, G. Utermann and G. Baier, “Physical Interaction of ApoE with Amyloid Precursor Protein Independent of the Amyloid Abeta Region in Vitro,” Journal of Biological Chemistry, Vol. 273, No. 22, 1998, pp. 13892-13897.
T. Ohshita, A. Nakatani and Y. Hiroi, “Purification by Column Chromatographies of Beta-Amyloid Precursor Proteins and Their Association with Other 95 kDa Protein in Rat Brain,” Journal of Chromatography B: Biomedical Sciences and Applications, Vol. 716, No. 1-2, 1998, pp. 107-118.
M. Trommsdorff, J. P. Borg, B. Margolis and J. Herz, “Interaction of Cytosolic Adaptor Proteins with Neuronal Apolipoprotein E Receptors and the Amyloid Precursor Protein,” Journal of Biological Chemistry, Vol. 273, No. 50, 1998, pp. 33556-33560.
J. P. Borg, S. W. Straight, S. M. Kaech, M. de Taddeo-Borg, D. E. Kroon, D. Karnak, R. S. Turner, S. K. Kim and B. Margolis, “Identification of an Evolutionarily Conserved Heterotrimeric Protein Complex Involved in Protein Targeting,” Journal of Biological Chemistry, Vol. 273, No. 48, 1998, pp. 31633-31636.
J. P. Borg, Y. Yang, M. De Taddeo-Borg, B. Margolis and R. S. Turner, “The X11Alpha Protein Slows Cellular Amyloid Precursor Protein Processing and Reduces Abeta40 and Abeta42 Secretion,” Journal of Biological Chemistry, Vol. 273, No. 24, 1998, pp. 14761-14766.
S.L. Sabo, L. M. Lanier, A. F. Ikin, O. Khorkova, S. Sahasrabudhe, P. Greengard and J. D. Buxbaum, “Regulation of Beta-Amyloid Secretion by FE65, an Amyloid Protein Precursor-Binding Protein,” Journal of Biological Chemistry, Vol. 274, No. 12, 1999, pp. 7952- 7957.
Z. Kouchi, H. Sorimachi, K. Suzuki and S. Ishiura, “Proteasome Inhibitors Induce the Association of Alzheimer’s Amyloid Precursor Protein with Hsc73,” Biochemical and Biophysical Research Communications, Vol. 254, No. 3, 1999, pp. 804-810.
K. Miyazaki, M. Hasegawa, K. Funahashi and M. Umeda, “A Metalloproteinase Inhibitor Domain in Alzheimer Amyloid Protein Precursor,” Nature, Vol. 362, No. 6423, 1993, pp. 839-841.
A. Odaka, T. Tsukahara, M. Momoi and T. Momoi, “c- jun Inhibited the Alternative Splicing of Neuron-Specific Amyloid Precursor Protein, but Stimulated the Non- Neuron Type One in P19 EC Cells,” Biochemical and Biophysical Research Communications, Vol. 206, No. 3, 1995, pp. 831-828.
D. Muller, H. Wiegmann, U. Langer, S. Motlzen-Lenz and R. M. Nitsch, “Lu 25-109, a Combined m1 Agonist and m2 Antagonist, Modulates Regulated Processing of the Amyloid Precursor Protein of Alzheimer’s Disease,” Journal of Neural Transmission, Vol. 105, No. 8-9, 1998, pp. 1029-1043. doi:10.1007/s007020050110
S. Rossner, U. Ueberham, R. Schliebs, J. R. Perez-Polo and V. Bigl, “The Regulation of Amyloid Precursor Protein Metabolism by Cholinergic Mechanisms and Neurotrophin Receptor Signaling,” Progress in Neurobio- logy, Vol. 56, No. 5, 1998, pp. 541-569.
B. Belandia, M. J. Latasa, A. Villa and A. Pascual, “Thyroid Hormone Negatively Regulates the Transcrip- tional Activity of the Beta-Amyloid Precursor Protein Gene,” Journal of Biological Chemistry, Vol. 273, No. 46, 1998, pp. 30366-30371.
R. K. Lee, S. Knapp and R. J. Wurtman, “Prostaglandin E2 Stimulates Amyloid Precursor Protein Gene Expres- sion: Inhibition by Immunosuppressants,” Journal of Neuroscience, Vol. 19, No. 3, 1999, pp. 940-947.
R. M. Nitsch, S. A. Farber, J. H. Growdon and R. J. Wurtman, “Release of Amyloid b-Protein Precursor Derivatives from Hippocampal Slices by Electrical Depolarization,” Proceedings of the National Acadamy of Sciences of the United States of America, Vol. 90, 1993, pp. 5191-5193.
J. G. Beeson, E. R. Shelton, H. W. Chan and F. H. Gage, “Differential Distribution of Amyloid Protein Precursor Immunoreactivity in the Rat Brain Studied by Using Five Different Antibodies,” Journal of Comparative Neurolo- gy, Vol. 342, No. 1, 1994, pp. 78-96.
J. P. Card, R. P. Meade and L. G. Davis, “Immunocyto- chemical Localization of the Precursor Protein for B- Amyloid in the Rat Central Nervous System,” Neuron, Vol. 1, No. 9, 1988, pp. 835-846.
T. Ohgami, T. Kitamoto and J. Tateishi, “The Rat Central Nervous System Expresses Alzheimer’s Disease Amyloid Precursor Protein APP695, but Not APP677 (L-APP form),” Journal of Neurochemistry, Vol. 61, No. 4, 1993, pp. 1553-1556.
C. Solá, G. Mengod, A. Probst and K. M. Palacios, “Differential Regional and Cellular Distribution of B- Amyloid Precursor Protein Messenger RNAs Containing and Lacking the Kunitz Protease Inhibitor Domain in the Brain of Human, Rat and Mouse,” Neuroscience, Vol. 53, 1993, pp. 267-295.
J. D. Buxbaum, G. Thinakaran, V. Koliatsos, J. O’Callahan, H. H. Slunt, D. L. Price and S. S. Sisodia, “Alzheimer Amyloid Protein Precursor in the Rat Hippocampus: Transport and Pressing through the Perforant Path,” Journal of Neuroscience, Vol. 18, 1998, pp. 9629-9637.
T. Kawarabayashi, M. Shoji, H. Yamaguchi, M. Tanaka, Y. Harigaya, K. Ishiguro and S. Hirai, “Amyloid β Protein Precursor Accumulates in Swollen Neurites Throughout Rat Brain with Aging,” Neuroscience Letters, Vol. 153, No. 1, 1993, pp. 73-76.
Y. Nakamura, M. Takeda, H. Niigawa, F. Kametani, S. Hariguchi, I. Yoshida, S. Kitajima and T. Nishimura, “Accumulation of Amyloid B-Protein Precursor (APP) in Purkinje Cells and Increase of Amino-Terminal Frag- ments of APP in Cerebrum and Cerebellum of Aged Rat Brain,” Brain Research, Vol. 643, No. 1-2, 1994, pp. 319- 323.
C. A. Sherman and G. A. Higgins, “Regulated Splicing of the Amyloid Precursor Protein during Postnatal Develop- ment of the Rat Basal Forebrain,” Developmental Brain Research, Vol. 66, No. 1, 1992, pp. 63-69.
J. V. Nadler, “Kainic Acid: Neurophysiological and Neurotoxic Actions,” Life Sciences, Vol. 24, No. 4, 1979, pp. 289-300. doi:10.1016/0024-3205(79)90325-4
R. Siman, J. P. Card, R. B. Nelson and L. G. Davis, “Expression of β-Amyloid Precursor Protein in Reactive Astrocytes Following Neuronal Damage,” Neuron, Vol. 3, No. 3, 1989, pp. 275-285.
T. Kawarabayashi, M. Shoji, Y. Harigaya, H. Tamaguchi and S. Hirai, “Expression of APP in the Early Stage of Brain Damage,” Brain Research, Vol. 563, No. 1-2, 1991, pp. 334-338.
C. Solá, F. J. Garcia-Ladona, G. Mengod, A. Probst, P. Frey and J. M. Palacios, “Increased Levels of the Kunitz Protease Inhibitor-Containing BAPP mRNAs in Rat Brain Following Neurotoxic Damage,” Molecular Brain Research, Vol. 17, 1993, pp. 41-52.
T. P. Wong, T. Debeir, K. Duff and A. C. Cuello, “Reorganization of Cholinergic Terminals in the Cerebral Cortex and Hippocampus in Transgenic Mice Carrying Mutated Presenilin-1 and Amyloid Precursor Protein Transgenes,” Journal of Neuroscience, Vol. 19, No. 7, 1999, pp. 2706-2716.
P. K. Panegyres, “The Effects of Excitotoxicity on the Expression of the Amyloid Precursor Protein Gene in the Brain and its Modulation by Neuroprotective Agents,” Journal of Neural Transmission, Vol. 105, No. 4-5, 1998, pp. 463-478.
P. K. Panegyres and J. Hughes, “The Neuroprotective Effects of the Recombinant Interleukin-1 Receptor An- tagonist rhIL-1ra after Excitotoxic Stimulation with Kainic Acid and its Relationship to the Amyloid Precursor Pro- tein Gene,” Journal of the Neurological Sciences, Vol. 154, No. 2, 1998, pp. 123-132.
B. Brugg, Y. L. Dubreuil, G. Huber, E. E. Wollman, N. Delhaye-Bouchaud and J. Mariani, “Inflammatory Pro- cesses Induce B-Amyloid Precursor Protein Changes in Mouse Brain,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, 199, pp. 3032-3035.
P. K. Panegyres, “A Study of the Relationship between Brain Seizure Activity, Immediate Early Genes and the Amyloid Precursor Protein Gene,” Ph.D Thesis, Universi- ty of Cambridge, Cambridge, 1995.
M. Walton, G. MacGibbon, D. Young, E. Sirimanne, C. Williams, P. Gluckman and M. Dragunow, “Do c-Jun, c- Fos, and Amyloid Precursor Protein Play a Role in Neuronal Death or Survival?” Journal of Neuroscience Re- search, Vol. 53, No. 3, 1998, pp. 330-342.
J. Trejo, T. Massamiri, T. Deng, N. N. Dewji, R. M. Bayney and J. H. Brown, “A Direct Role for Protein Kinase C and the Transcription Factor jun/AP-1 in the Regulation of the Alzheimer’s B-amyloid Precursor Protein Gene,” Journal of Biological Chemistry, Vol. 269, No. 34, 1994, pp. 21682-21690.
K. Iverfeldt, S. I. Walaas and P. Greengard, “Altered Processing of Alzheimer Amyloid Precursor Protein in Response to Neuronal Degeneration,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 9, 1993, pp. 4146-4150.
W. Wallace, S. T. Ahlers, J. Gotlib, V. Bragin, J. Sugar, R. Gluck, P. A. Shea, K. L. Davis and V. Haroutunian, “Amyloid Precursor Protein in the Cerebral Cortex is Rapidly and Persistently Induced by Loss of Subcortical Innervation,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 18, 1993, pp. 8712-8716.
Y. Nakamura, M. Takeda, H. Niigawa, S. Hariguchi and T. Nishimura, “Amyloid B-Protein Deposition in Rat Hippocampus Lesioned by Ibotenic Acid Injection,” Neuroscience Letters, Vol. 136, 1992, pp. 95-98.
K. Shigematsu, P. L. McGeer, D. G. Walker, T. Ishii and E. G. McGeer, “Reactive Microglia/Macrophages Phago- cytose Amyloid Precursor Protein Produced by Necrosis Following Neuronal Damage,” Journal of Neuroscience Research, Vol. 31, 1992, pp. 443-453.
J. B. Pan, L. M. Monteggia and T. Giordano, “Altered Levels and Splicing of the Amyloid Precursor Protein in the Adult Rat Hippocampus After Treatment with DMSO or Retinoic Acid,” Molecular Brain Research, Vol. 18, No. 3, 1993, pp. 259-266.
A. Lewen, G. L. Li, P. Nilsson, Y. Olsson and L. Hillered, “Traumatic Brain Injury in Rat Produces Changes of B- Amyloid Precursor Protein Immunoreactivity,” NeuroRe- port, Vol. 6, 1995, pp. 357-360.
N. Murakami, T. Yamaki, Y. Iwamoto, T. Sakakibara, N. Kobori, S. Fushiki and S. Ueda, “Experimental Brain Injury Induces Expression of Amyloid Precursor Protein, which May be Related to Neuronal Loss in the Hi- ppocampus,” Journal of Neurotrauma, Vol. 15, No. 11, 1998, pp. 993-1003.
N. Otsuko, M. Tamonaga and K. Ikeda, “Rapid Appea- rance of B-Amyloid Precursor Protein Immunore- activity in Damaged Axons and Reactive Glial Cells in Rat Brain Following Needle Stab Injury,” Brain Research, Vol. 568, No. 1-2, 1991, pp. 35-338.
C. Van Den Heuvel, S. Lewis, M. Wong, J. Manavis, J. Finnie, P. Blumbergs, N. Jones and P. Reilly, “Diffuse Neuronal Perikaryon Amyloid Precursor Protein Immu- noreactivity in a Focal Head Impact Model,” Acta Neuro- chirurgica Supplementum, Vol. 71, 1998, pp. 209-211.
K. Abe, R. E. Tanzi and K. Kogure, “Selective Induction of Kunitz Type Protease Inhibitor Domain Containing Amyloid Precursor Protein mRNA after Persistent Focal Ischemia,” Neuroscience Letters, Vol. 125, No. 2, 1991, pp. 172-174.
K. Baiden-Amissah, U. Joashi, R. Blumberg, H. Mehmet, A. D. Edwards and P. M. Cox, “Expression of Amyloid Precursor Protein (Beta-APP) in the Neonatal Brain Following Hypoxic Ischaemic Injury,” Neuropathology and Applied Neurobiology, Vol. 24, No. 5, 1998, pp. 346- 352.
D. T. Stephenson, K. Rash and J. A. Clemens, “Amyloid Precursor Protein Accumulates in Regions of Neurodege- neration Following Focal Cerebral Ischemia in the Rat,” Brain Research, Vol. 593, No. 1,1992, pp. 128-135. doi:10.1016/0006-8993(92)91274-I
H. Wakita, H. Tomimoto, I. Akiguchi, K. Ohnishi, S. Nakamura and J. Kimura, “Regional Accumulation of Amyloid B/A4 Protein Precursor in the Gerbil Brain Following Transient Cerebral Ischemia,” Neuroscience Letters, Vol. 146, 1992, pp. 135-138.
H. Tomimoto, H. Wakita, I. Akiguchi, S. Nakamura and J. Kimura, “Temporal Profiles of Accumulation of Amyloid B/A4 Protein Precursor in the Gerbil after Graded Ischemic Stress,” Journal of Cerebral Blood Flow and Metabolism, Vol. 14, No. 4, 1994, pp. 565-573.
G. Palacios, G. Mengod, A. Tortosa, I. Ferrer and J. M. Palacios, “Increased B-Amyloid Precursor Protein Ex- pression in Astrocytes in the Gerbil Hippocampus Fo- llowing Ischaemia: Association with Proliferation of Astrocytes,” European Journal of Neuroscience, Vol. 7, 1995, pp. 501-510.
M. J. McNamara, C. T. Ruff, W. Wasco, R. E. Tanzi, G. Thinakaran and B. T. Hyman, “Immunohistochemical and In Situ Analysis of Amyloid Precursor-like Protein-1 and Amyloid Precursor-like Protein-2 Expression in Alzhei- mer Disease and Aged Control Brains,” Brain Research, Vol. 804, No. 1, 1998, pp. 45-51.
K. Plaschke, E. Martin and H. J. Bardenheuer, “Effect of Propentofylline on Hippocampal Brain Energy State and Amyloid Precursor Protein Concentration in a Rat Model of Cerebral Hypoperfusion,” Journal of Neural Transmis- sion, Vol. 105, 1998, pp. 1065-1077.
J. N. Scott, I. M. Parhad and A. W. Clark, “B-Amyloid Precursor Protein Gene is Differentially Expressed in Axotomized Sensory and Motor Systems,” Molecular Brain Research, Vol. 10, No. 4, 1991, pp. 315-325.
J. Alvarez, R. D. Moreno, O. Llanos, N. C. Inestrosa, E. Brandan, T. Colby and F. S. Esch, “Axonal Sprouting Induced in the Sciatic Nerve by the Amyloid Precursor Protein (APP) and Other Antiproteases,” Neuroscience Letters, Vol. 144, No. 1-2, 1992, pp. 130-134.
O. Salinero, J. J. Garrido and F. Wandosell, “Amyloid Precursor Protein Proteoglycan is Increased after Brain Damage,” Biochimica et Biophysica Acta, Vol. 1406, No. 3, 1998, pp. 237-250.
J. Alvarez, R. D. Moreno and N. C. Inestrosa, “Mitosis of Schwann Cells and Demyelination are Induced by the Amyloid Precursor Protein and Other Protease Inhibitors in the Rat Sciatic Nerve,” European Journal of Neuroscience, Vol. 7, No. 1, 1995, pp. 152-159.
G. Forloni, R. Del Bo, N. Angeretti, S. Smiroldo, N. Gabellini and G. Vantini, “Nerve Growth Factor Does Not Influence the Expression of B Amyloid Precursor Protein mRNA in Rat Brain: In Vivo and in Vitro Studies,” Brain Research, Vol. 620, No. 2, 1993, pp. 292-296.
M. D. Lindner, S. I. Dworetzky, C. Sampson and R. Loy, “Relationship of APP mRNA Transcripts and Levels of NGF and Low-Affinity NGF Receptors to Behavioral Measures of Age-related Cognitive Dysfunction,” Journal of Neurosciemce, Vol. 14, No. 4, 1994, pp. 2282-2289.
H. Zheng, M. Jiang and M. E. Trumbauer, “β-amyloid Precursor Protein-deficient Mice Show Reactive Gliosis and Decreased Locomotor Activity,” Cell, Vol. 81, No. 4, 1995, pp. 525-531.
H. Zheng, M. Jiang, M. E. Trumbauer, R. Hopkins, D. J. Sirinathsinghji, K. A. Stevens, M. W. Conner, H. H. Slunt, S. S. Sisodia, H. Y. Chen and L. H. Van der Ploeg, “Mice Deficient for the Amyloid Precursor Protein Gene,” Annals of the New York Academy of Sciences, Vol. 777, No. 908, 1996, pp. 421-426.
U. Muller, N. Cristina, Z. W. Li, D. P. Wolfer, H. P. Lipp, T. Rulicke, S. Brandner, A. Aguzzi and C. Weissmann, “Behavioral and Anatomical Deficits in Mice Homozy- gous for a Modified B-amyloid Precursor Protein Gene,” Cell, Vol. 79, No. 5, 1994, pp. 755-765.
U. Muller, N. Cristina, Z. W. Li, D. P. Wolfer, H. P. Lipp, T. Rulicke, S. Brandner, A. Aguzzi and C. Weissman, “Mice Homozygous for a Modified Beta-amyloid Precursor Protein (Beta APP) Gene Show Impaired Behaviour and High Incidence of Agenesis of the Corpus Callosum,” Annals of the New York Academy of Sciences, Vol. 777, 1996, pp. 65-73.
C. S. von Koch, H. Zheng, H. Chen, M. Trumbauer, G. Thinakaran, L. G. van der Ploeg, D. L. Price and S. S. Sisodia, “Generation of APLP2 KO Mice and Early Postnatal Lethality in APLP2/APP Double KO Mice,” Neurobiology of Aging, Vol. 18, No. 6, 1997, pp. 661- 669.
R. G. Perez, H. Zheng, L. H. T. Van der Ploeg and E. H. Koo, “The B-amyloid Precursor Protein of Alzheimer’s Disease Enhances Neuron Viability and Modulates Neuronal Polarity,” Journal of Neuroscience, Vol. 17, 1997, pp. 9407-9414.
G. R. Dawson, G. R. Seabrook, H. Zheng, D. W. Smith, S. Graham, G. O’Dowd, B. J. Bowery, S. Boyce, M. E. Trumbauer, H. Y. Chem, L. H. Van der Ploeg and D. J. Sirinathsinghji, “Age-related Cognitive Deficits, Impaired Long-term Potentiation and Reduction in Synaptic Marker Density in Mice Lacking the Beta-amyloid Precursor Protein,” Neuroscience, Vol. 90, No. 1, 1999, pp. 1-13.
H. Meziane, J. C. Dodart, C. Mathis, S. Little, J. Clemens, S. M. Paul and A. Ungerer, “Memory-Enhancing Effects of Secreted Forms of the B-amyloid Precursor Protein in Normal and Amnestic Mice,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, 1998, pp. 12683-12688.
J. M. Roch, E. Masliah, A. C. Roch-Levecq, M. P. Sundsmo, D. A. Otero, I. Veinbergs and T. Saitoh, “Increase of Synaptic Density and Memory Retention by a Peptide Representing the Trophic Domain of the Amyloid Beta/A4 Protein Precursor,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 16, 1994, pp. 7450-7454.
L. S. Higgins, D. M. Holtzman, J. Rabin, W. C. Mobley and B. Cordell, “Transgenic Mouse Brain Histopathology Resembles Early Alzheimer’s Disease,” Annals of Neurology, Vol. 35, No. 5, 1994, pp. 598-607.
D. Games, D. Adams, R. Alessandrini, R. Barbour, P. Berthelette, C. Blackwell, T. Carr, J. Clemens, T. Donaldson and F. Gillespie, “Alzheimer-type Neuropa- thology in Transgenic Mice Overexpressing V717F B- amyloid Precursor Protein,” Nature, Vol. 373, No. 6514, 1995, pp. 523-527.
K. S. Chen, E. Masliah, H. Grajeda, T. Guido, J. Huang, K. Khan, R. Motter, F. Soriano and D. Games, “Neuro- degenerative Alzheimer-like Pathology in PDAPP 717V --> F Transgenic Mice,” Progress in Brain Research, Vol. 117, 1998, pp. 327-334.
C. Czech, C. Masters and K. Beyreuther, “Alzheimer’s Disease and Transgenic Mice,” Journal of Neural Transmission, Vol. 44 Suppl, 1994, pp. 219-230.
C. Czech, P. Delaere, A. F. Macq, M. Reibaud, S. Dreisler, N. Touchet, B. Schombert, M. Mazadier, L. Mercken, M. Theisen, L. Pradier, J. N. Octave, K. Beyreuther and G. Tremp, “Proteolytical Processing of Mutated Human Amyloid Precursor Protein in Transgenic Mice,” Mo- lecular Brain Research, Vol. 47, No. 1-2, 1997, pp. 108- 116.
K. K. Hsiao, D. R. Borchelt, K. Olson, R. Johannsdottir, C. Kitt, W. Yunis, S. Xu, C. Eckman, S. Younkin and D. Price, “Age-related CNS Disorder and Early Death in Transgenic FVB/N Mice Overexpressing Alzheimer Amyloid Precursor Proteins,” Neuron, Vol. 15, No. 5, 1995, pp. 1203-1218.
K. Hsiao, P. Chapman, S. Nilsen, C. Eckman, Y. Harigaya, S. Younkin, F. Yang and G. Cole, “Correlative Memory Deficits, A Beta Elevation, and Amyloid Plaques in Transgenic Mice,” Science, Vol. 27, 1996, pp. 99-102.
M. C. Irizarry, F. Soriano, M. McNamara, K. J. Page, D. Schenk, D. Games and B. T. Hyman, “Abeta Deposition is Associated with Neruophil Changes, but Not with Overt Neuronal Loss in the Human Amyloid Precursor Protein V717F (PDAPP) Transgenic Mouse,” Journal of Neuroscience, Vol. 17, 1997, pp. 7053-7059.
G. Leanza, “Chronic Elevation of Amyloid Precursor Protein Expression in the Neocortex and Hippocampus of Rats with Selective Cholinergic Lesions,” Neuroscience Letters, Vol. 257, No. 1, 1998, pp. 53-56.
J. F. Loring, C. Paszty, A. Rose, T. K. McIntosh, H. Murai, J. E. Pierce, S. R. Schramm, K. Wymore, V. M. Lee, J. Q. Trojanowski and K. R. Peterson, “ Rational Design of an Animal Model for Alzheimer’s Disease: Introduction of Multiple Human Genomic Transgenes to Reproduce AD Pathology in a Rodent,” Neurobiology of Aging, Vol. 17, No. 2, 1996, pp. 173-182.
D. Moechars, K. Lorent, I. Dewachter, V. Baekelandt, B. De Strooper and F. Van Leuven, “Transgenic Mice Expressing an Alpha-secretion Mutant of the Amyloid Precursor Protein in the Brain Develop a Progressive CNS Disorder,” Behavioural Brain Research, Vol. 95, No. 1, 1998, pp. 55-64.
L. Mucke, E. Masliah, W. B. Johnson, M. D. Ruppe, M. Alford, E. M. Rockenstein, S. Forss-Petter, M. Pietropaolo, M. Mallory and C. R. Abraham, “Synaptotrophic Effects of Human Amyloid B Protein Precursors in the Cortex of Transgenic Mice,” Brain Research, Vol. 666, 1994, pp. 151-167.
L. Mucke, C. R. Abraham and E. Masliah, “Neurotrophic and Neuroprotective Effects of hAPP in Transgenic Mice,” Annals of the New York Academy of Sciences, Vol. 777, No. 617, 1996, pp. 82-88.
I. Nishimura, T. Uetsuki, S. U. Dani, Y. Ohsawa, I. Saito, H. Okamura, Y. Uchiyama and K. Yoshikawa, “Degene- ration in Vivo of Rat Hippocampal Neurons by Wild-type Alzheimer Amyloid Precursor Protein Overexpressed by Adenovirus-mediated Gene Transfer,” Journal of Neuro- science, Vol. 18, 1998, pp. 2387-2398.
S. Rabizadeh, C. M. Bitler, L. L. Butcher and D. E. Bredesen, “Expression of the Low-affinity Nerve Growth Factor Receptor Enhances B-amyloid Peptide Toxicity,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 22, 1994, pp. 10703-10706.
M. Racchi, J. A. Johnston, F. M. Flood, R. F. Cowburn and S. Govoni, “Amyloid Precursor Protein Metabolism in Fibroblasts from Individuals with One, Two or Three Copies of the Amyloid Precursor Protein (APP) Gene,” Biochemical Journal, Vol. 338, 1999, pp. 777-782.
F. A. Sandhu, M. Salim and S. B. Zain, “Expression of the Human Beta-amyloid Protein of Alzheimer’s Disease Specifically in the Brains of Transgenic Mice,” Journal of Biological Chemistry, Vol. 266, No. 32, 1991, pp. 21331- 21334.
C. Sturchler-Pierrat, D. Abramowski, M. Duke, K. H. Wiederhold, C. Mistl, S. Rothacher, B. Ledermann, K. Burki, P. Frey, P. A. Paganetti, C. Waridel, M. E. Calhous, M. Jucker, A. Prosbst, M. Staufenbiel and B. Sommer, “Two Amyloid Precursor Protein Transgenic Mouse Models with Alzheimer Disease-like Pathology,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 24, 1997, pp. 13287- 13292.
F. Yamaguchi, S. J. Richards, K. Beyreuther, M. Salbaum, G. A. Carlson and S. B. Dunnett, “Transgenic Mice for the Amyloid Precursor Protein 695 Isoform Have Impaired Spatial Memory,” NeuroReport, Vol. 2, No. 12, 1991, pp. 781-784.
G. A. Carlson, D. R. Brochelt, A. Dake, S. Turner, V. Danielson, J. D. Coffin, C. Eckman, J. Meiners, S. P. Nilsen, S. G. Younkin and K. K. Hsiao, “Genetic Modification of the Phenotypes Produced by Amyloid Precursor Protein Overexpression in Transgenic Mice,” Human Molecular Genetics, Vol. 6, No. 11, 1997, pp. 1951-1959.
C. Schonlein, A. Probst and G. Huber, “Characterization of Proteases with the Specificity to Cleave at the Secretase-site of Beta-APP,” Neuroscience Letters, Vol. 161, No. 1, 1993, pp. 33-36.
D. Moechars, M. Gilis, C. Kuiperi, I. Laenen and F. Van Leuven, “Aggressive Behaviour in Transgenic Mice Ex- pressing APP is Alleviated by Serotonergic Drugs,” Neuro- Report, Vol. 9, No. 16, 1998, pp. 3561-3564.
F. A. Sandhu, R. H. Porter, R. V. Eller, S. B. Zain, M. Salim and J. T. Greenamyre, “NMDA and AMPA Re- ceptors in Transgenic Mice Expressing Human Beta- Amyloid Protein,” Journal of Neurochemistry, Vol. 61, 1993, pp. 2286-2289.
D. Moechars, K. Lorent, B. De Strooper, I. Dewachter and F. Van Leuven, “Expression in Brain of Amyloid Precursor Protein Mutated in the Alpha-secretase Site Causes Disturbed Behaviour, Neuronal Degeneration and Premature Death in Transgenic Mice,” EMBO Journal, Vol. 15, No. 6, 1996, pp. 1265-1274.
D. S. Howland, S. P. Trusko, M. J. Savage, A. G. Reaume, D. M. Lang, J. D. Hirsch, N. Maeda, R. Siman, B. D. Greenberg, R. W. Scott and D. G. Flood, “Modulation of Secreted Beta-Amyloid Precursor Protein and Amyloid Beta-Peptide in Brain by Cholesterol,” Journal of Bio- logical Chemistry, Vol. 273, No. 26, 1998, pp. 16576- 16582.
S. A. Frautschy, F. Yang, M. Irrizarry, B. Hyman, T. C. Saido, K. Hsiao and G. M. Cole, “Microglial Response to Amyloid Plaques in APPsw Transgenic Mice,” American Journal of Pathology, Vol. 152, No. 1, 1998, pp. 307-317.
T. A. Bayer, A. Fossgreen, C. Czech, K. Beyreuther and O. D. Wiestler, “Plaque Formation in Brain Transplants Exposed to Human Beta-amyloid Precursor Protein 695,” Acta Neuropathologica, Vol. 92, No. , 1996, pp. 130-137.
T. Arendt, M. Holzer, R. Fruth, M. K. Bruckner and U. Gartner, “Paired Helical Filament-like Phosphorylation of Tau, Deposition of Beta/A4-amyloid and Memory Im- pairment in Rat Induced by Chronic Inhibition of Phos- phatase 1 and 2A,” Neuroscience, Vol. 69, No. 3, 1995, pp. 691-698.
R. B. Banati, J. Gehrmann, J. Lannes-Vieira, H. Wekerle and G. W. Kreutzberg, “Inflammatory Reaction in Ex- perimental Autoimmune Encephalomyelitis (EAE) is Accompanied by a Microglial Expression of the Beta A4-amyloid Precursor Protein (APP),” Glia, Vol. 14, No. 3, 1995, pp. 209-215.
J. Shi, K. S. Panickar, S. H. Yang, O. Rabbani, A. L. Day and J. W. Simpkins, “Estrogen Attenuates Over- expression of Beta-amyloid Precursor Protein Messager RNA in an Animal Model of Focal Ischemia,” Brain Research, Vol. 810, No. 1-2, 1998, pp. 87-92.
A. Islam, R. N. Kalaria, B. Winblad and A. Adem, “En- hanced Localization of Amyloid Beta Precursor Protein in the Rat Hippocampus Following Long-Term Adre- nalectomy,” Brain Research, Vol. 806, 1998, pp. 108- 112.
H. M. Chao, R. L. Spencer, M. Frankfurt and B. S. McEwen, “The Effects of Aging and Hormonal Manipulation on Amyloid Precursor Protein APP 695 mRNA Expression in the Rat Hippocampus,” Journal of Neuroendocrinology, Vol. 6, 1994, pp. 517-521.
T. Tully and K. White, “Human Amyloid Precursor Protein Ameliorates Behavioural Deficit of Flies Deleted for Appl Gene,” Neuron, Vol. 9, 1992, pp. 595-605.
L. Torroja, L. Luo and K. White, “APPL, the Drosophila Member of the APP-family, Exhibits Differential Tra- fficking and Processing in CNS Neurons,” Journal of Neuroscience, Vol. 16, No. 15, 1996, pp. 4638-4650.
A. Fossgreen, B. Bruckner, C. Czech, C. L. Masters, K. Beyreuther and R. Paro, “Transgenic Drosophila Express- ing Human Amyloid Precursor Protein Show Gamma- secretase Activity and a Blistered-Wing Phenotype,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, 1998, pp. 13703- 13708.
I. Daigle and C. Li, “Apl-1, a Caenorhabditis Elegans Gene Encoding a Protein Related to the Human Beta- amyloid Protein Precursor,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 24, 1993, pp. 12045-12049.
A. I. Bush, W. H. Pettingal, G. Multhaup, M. D. Paradis, J. P. Vonsattel, J. F. Gusella, K. Beyreuther, C. L. Masters and R. E. Tanzi, “Rapid Induction of Alzheimer AB Amyloid Formation by Zinc,” Science, Vol. 265, 1994, pp. 1464-1467.
N. Ida, T. Hartmann, J. Pantel, J. Schroder, R. Zerfass, H. Forstl, R. Sandbrink, C. L. Masters and K. Beyreuther, “Analysis of Heterogeneous A4 Peptides in Human Cere- brospinal Fluid and Blood by a Newly Developed Sensitive Western Blot Assay,” Journal of Biological Chemistry, Vol. 271, No. 37, 1996, pp. 22908-22914.
M. Simons, B. De Strooper, G. Multhaup, P. J. Tienari, C. G. Dotti and K. Beyreuther, “Amyloidogenic Processing of the Human Amyloid Precursor Protein in Primary Cultures of Rat Hippocampal Neurons,” Journal of Neuroscience, Vol. 16, No. 3, 1996, pp. 899-908.
C. Vigo-Pelfrey, D. Lee, P. Keim, I. Lieberburg and D. B. Schenk, “Characterization of B-amyloid Peptide From Human Cerebrospinal Fluid,” Journal of Neurochemistry, Vol. 61, 1993, pp. 1965-1968.
G. K. Gouras, H. Xu, J. N. Jovanovic, J. D. Buxbaum, R. Wang, P. Greengard, N. R. Relkin and S. Gandy, “Gene- ration and Regulation of Beta-amyloid Peptide Variants by Neurons,” Journal of Neurochemistry, Vol. 71, No. 5, 1998, pp. 1920-1925.
C. J. Pike, A. J. Walencewicz-Wasserman, J. Kosmoski, D. H. Cribbs, C. G. Glabe and C. W. Cotman, “Structure- activity Analyses of B-amyloid Peptides: Contributions of the B25-35 R and Neurotoxicity,” Journal of Neuroche- mistry, Vol. 64, 1995, pp. 253-265.
C. J. Barrow, A. Yasuda, P. T. Kenny and M. G. Zagorski, “Solution Conformations and Aggregational Properties of Synthetic Amyloid Beta-peptides of Alzheimer’s Disease. Analysis of Circular Dichroism Spectra,” Journal of Molecular Biology, Vol. 225, No. 4, 1992, pp. 1075- 1093.
D. Burdick, B. Soreghan, M. Kwon, J. Kosmoski, M. Knauer, A. Henschen, J. Yates, C. Cotman and C. Glabe, “Assembly and Aggregation Properties of Synthetic Alzh- eimer’s A4/beta Amyloid Peptide Analogs,” Journal of Biological Chemistry, Vol. 267, No. 1, 1992, pp. 546- 554.
P. E. Fraser, J. T. Nguyen, W. K. Surewicz and D. A. Kirschner, “PH-Dependent Structural Transitions of Alzheimer Amyloid Peptides,” Biophysical Journal, Vol. 60, No. 5, 1991, pp. 1190-1201.
C. Soto, M. C. Branes, J. Alvarez and N. C. Inestrosa, “Structural Determinants of the Alzheimer’s Amyloid Beta-Peptide,” Journal of Neurochemistry, Vol. 63, No. 4, 1994, pp. 1991-1198.
H. Stricht, P. Bayer, D. Willbold, S. Dames, C. Hilbich, K. Beyreuther, R. W. Frank and P. Rosch, “Structure of Amyloid A4-(1-40)-peptide of Alzheimer’s Disease,” European Journal of Biochemistry, Vol. 233, No. 1, 1995, pp. 293-298.
F. P. Zemlan, G. D. Vogelsang, L. McLaughlin and G. E. Dean, “Alzheimer’s Paired Helical Filaments: Amyloid Precursor Protein Epitope Mapping,” Brain Research Bulletin, Vol. 33, No. 4, 1994, pp. 387-392.
C. Hilbich, B. Kisters-Woike, J. Reed, C. L. Masters and K. Beyreuther, “Human and Rodent Sequence Analogs of Alzheimer’s Amyloid Beta A4 Share Similar Properties and Can be Solubilized in Buffers of pH 7.4,” European Journal of Biochemistry, Vol. 201, No. 1, 1991, pp. 61- 69.
B. De Strooper, M. Simons, G. Multhaup, F. Van Leuven, K. Beyreuther and C. G. Dotti, “Production of Intracellu- lar Amyloid-Containing Fragments in Hippocampal Neurons Expressing Human Amyloid Precursor Protein and Protection Against Amyloidogenesis by Subtle Amino Acid Substitutions in the Rodent Sequence,” EMBO Journal, Vol. 14, No. 20, 1995, pp. 4932-4938.
P. E. Fraser, J. T. Nguyen, H. Inouye, W. K. Surewicz, D. J. Selkoe, M. B. Podlisny and D. A. Kirschner, “Fibril Formation by Primate, Rodent, and Dutch-Hemorrhagic Analogues of Alzheimer Amyloid Beta-Protein,” Bioche- mistry, Vol. 31, No. 44, 1992, pp. 10716-10723.
G. A. Higgins, D. A. Lewis, S. Bahmanyar, D. Goldgaber, D. C. Gajdusek, W. G. Young, J. H. Morrison and M. C. Wilson, “Differential Regulation of Amyloid-b-protein mRNA Expression within Hippocampal Neuronal Sub- populations in Alzheimer Disease,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 85, 1988, pp. 1297-1301.
L. Otvos Jr, G. I. Szendrei, V. M. Lee and H. H. Mantsch, “Human and Rodent Alzheimer Beta-Amyloid Peptides Acquire Distinct Conformations in Membrane-Mimicking Solvents,” European Journal of Biochemistry, Vol. 211, No. 1-2, 1993, pp. 249-257.
M. D. Fowler, A. V. Koulov, C. Alory-Jost, M. S. Marks, W. E. Balch and J. W. Kelly, “Functional Amyloid Formation with Mammalian Tissue,” PLoS Biology, Vol. 4, No. 1, 2006, p. e6.
S. J. Wood, R. Wetzel, J. D. Matin and M. R. Hurle, “Prolines and Amyloidogenicity in Fragments of the Alzheimer’s Peptide Beta/A4,” Biochemistry, Vol. 34, No. 3, 1995, pp. 724-730.
T. Wisniewski, J. Ghiso and B. Frangione, “Peptides Homologous to the Amyloid Protein of Alzheimer’s Disease Containing a Glutamine for Glutamic Acid Substitution Have Accelerated Amyloid Fibril Formation,” Biochemical and Biophysical Research Communications, Vol. 179, No. 3, 1991, pp. 1247-1254.
W. J. Strittmatter, D. Y. Huang, R. Bhasin, A. D. Roses and D. Goldgaber, “Avid Binding of Beta A Amyloid Peptide to its Own Precursor,” Experimental Neurology, Vol. 122, No. 2, 1993, pp. 327-334.
D. Huang, M. Martin, D. Hu, A. D. Roses, D. Goldgaber and W. J. Strittmatter, “Binding of IgG to Amyloid Beta A4 Peptide via the Heavy-chain Hinge Region with Preservation of Antigen Binding,” Journal of Neuroim- munology, Vol. 48, No. 2, 1993, pp. 199-203.
L. K. Rasmussen, E. S. Sorensen, T. E. Petersen, J. Gliemann and P. H. Jensen, “Identification of Glutamine and Lysine Residues in Alzheimer Amyloid Beta A4 Pep- tide Responsible for Transglutaminase-Catalysed Homo- polymerization and Cross-Linking to Alpha 2M Receptor,” FEBS Letters, Vol. 338, No. 2, 1994, pp. 161-166.
J. Y. Koh, L. L. Yang and C. W. Cotman, “β-amyloid Protein Increases the Vulnerability of Cultured Cortical Neurons to Excitotoxic Damage,” Brain Research, Vol. 533, No. 2, 1990, pp. 315-320. doi:10.1016/0006-8993(90)91355-K
B. A. Yankner, L. K. Duffy and D. A. Kirschner, “Neuro- trophic and Neurotoxic Effects of Amyloid β Protein: Re- versal by Tachykinin Neuropeptides,” Science, Vol. 250, No. 4978, 1990, pp. 279-282.
P. Rovero, R. Patacchini, A. R. Renzetti, M. Brown, J. Mizrahi, C. A. Maggi and A. Giachetti, “Interaction of Amyloid B Protein (25 - 35) with Tachykinin Receptors,” Neuropeptides, Vol. 22, 1992, pp. 99-101.
Y. Shimohigashi, H. Matsumoto, Y. Takano, R. Saito, T. Iwara, H. O. Kamiya and M. Ohno, “Receptor-mediated Specific Biological Activity of a β-Amyloid Protein Fragment for NK-1 Substance P Receptors,” Biochemical and Biophysical Research Communications, Vol. 193, No. 2, 1993, pp. 624-630.
V. K. Singh, J. F. Cheng and S. J. C. Leu, “Effect of Substance P and Protein Kinase Inhibitors on β-Amyloid Peptide-Induced Proliferation of Cultured Brain Cells,” Brain Research, Vol. 660, No. 2, 1994, pp. 353-356.
H. Kimura and D. Schubert, “Amyloid β-protein Activates Tachykinin Receptors and Inositol Triphosphate Accu- mulation by Synergy with Glutamate,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, 1993, pp. 7508-7512.
L. D. Plant, J. P. Boyle, I. F. Smith, C. Peers and H. A. Pearson, “The Production of Amyloid Beta Peptide is a Critical Requirement for the Viability of Central Neurons,” Journal of Neuroscience, Vol. 23, No. 13, 2003, pp. 5531- 5535.
F. Kamenetz, T. Tomita, H. Hsieh, G. Seabrook, D. Borchelt, T. Iwatsubo, S. Sisodia and R. Malinow, “APP Processing and Synaptic Function,” Neuron, Vol. 37, No. 6, 2003, pp. 925-937.
Z. Khalil, H. Chen and R. D. Helme, “Mechanisms Underlying the Vascular Activity of Beta-amyloid Protein Fragment (beta A(4)25-35) at the Level of Skin Micro- vasculature,” Brain Research, Vol. 736, No. 1-2, 1996, pp. 206-216.
N. S. Cheung, D. H. Small and B. G. Livett, “An Amyloid Peptide, Beta A4 25-35, Mimics the Function of Substance P on Modulation of Nicotine-Evoked Secretion and Desensitization in Cultured Bovine Adrenal Chroma- ffin Cells,” Journal of Neurochemistry, Vol. 60, No. 3, 1993, pp. 1163-1166. doi:10.1111/j.1471-4159.1993.tb03270.x
J. F. Kelly, K. Furukawa, S. W. Barger, M. R. Rengen, R. J. Mark, E. M. Blanc, G. S. Roth and M. P. Mattson, “Amyloid Beta-peptide Disrupts Carbachol-induced Mus- carinic Cholinergic Signal Transduction in Cortical Neurons,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 13, 1996, pp. 6753- 6758.
M. P. Mattson, B. Cheng, D. Davis, K. Bryant, I. Lieberburg and R. E. Rydel, “B-amyloid Peptides De- stabilize Calcium Homeostasis and Render Human Cor- tical Neurons Vulnerable to Excitotoxicity,” Journal of Neuroscience, Vol. 12, No. 2, 1992, pp. 376-389.
M. P. Mattson, B. Cheng, A. R. Culwell, F. S. Esch, I. Lieberburg and R. E. Rydel, “Evidence for Excitoprotec- tive and Intraneuronal Calcium-regulating Roles for Secreted Forms of the B-amyloid Precursor Protein,” Neuron, Vol. 10, 1993, pp. 243-254.
B. Stix and G. Reiser, “Beta-Amyloid Peptide 25-35 Re- gulates Basal and Hormone-Stimulated Ca2+ Levels in Cultured Rat Astrocytes,” Neuroscience Letters, Vol. 243, No. 1-3, 1998, pp. 121-124.
V. Meske, U. Hamker, F. Albert and T. G. Ohm, “The Effects of Beta/A4-amyloid and Its Fragments on Calcium Homeostasis, Glial Fibrillary Acidic Protein and S100 beta Staining, Morphology and Survival of Cultured Hi- ppocampal Astrocytes,” Neuroscience, Vol. 85, No. 4, 1998, pp. 1151-1160.
Y. Goodman and M. P. Mattson, “Ceramide Protects Hippocampal Neurons against Excitotoxic and Oxidative Insults, and Amyloid Beta-peptide Toxicity,” Journal of Neurochemistry, Vol. 66, No. 2, 1996, pp. 869-872.
V. Silei, C. Fabrizi, G. Venturini, M. Salmona, O. Bugiani, F. Tagliavini and G. M. Lauro, “Activation of Microglial Cells by PrP and Beta-amyloid Fragments Raises Intra- cellular Calcium through L-Type Voltage Sensitive Cal- cium Channels,” Brain Research, Vol. 818, 1999, pp. 168-170.
S. Haga, K. Ikeda, M. Sato and T. Ishii, “Synthetic Alzheimer Amyloid Beta/A4 Peptides Enhance Produc- tion of Complement C3 Component by Cultured Micro- glial Cells,” Brain Research, Vol. 601, 1993, pp. 88-94.
C. Behl, J. B. Davis, R. Lesley and D. Schubert, “Hy- drogen Peroxide Mediates Amyloid B Protein Toxicity,” Cell, Vol. 77, No. 6, 1994, pp. 817-827.
M. E. Harris, K. Hensley, D. A. Butterfield, R. A. Leedle and J. M. Carney, “Direct Evidence of Oxidative Injury Produced by the Alzheimer’s β-Amyloid Peptide (1-40) in Cultured Hippocampal Neurons,” Experimental Neu- rology, Vol. 131, No. 2, 1995, pp. 193-202.
D. Schubert, C. Behl, A. Brack, R. Dargusch, Y. Sagara and H. Kimura, “Amyloid Peptides are Toxic Via a Common Oxidative Mechanism,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 6, 1995, pp. 1989-1993.
C. Behl, J. B. Davis, F. G. Klier and D. Schubert, “Amyloid B Peptide Induces Necrosis Rather Than Apoptosis,” Brain Research, Vol. 645, 1994, pp. 253- 264.
Y. P. Li, A. F. Bushnell, C. M. Lee, L. S. Perlmutter and S. K. Wong, “Beta-Amyloid Induces Apoptosis in Human-Derived Neurotypic SH-SY5Y Cells,” Brain Re- search, Vol. 738, No. 2, 1996, pp. 196-204.
W. Pike and C. W. Cotman, “Calretinin-Immunoreactive Neurons are Resistant to β-Amyloid Toxicity in Vitro,” Brain Research, Vol. 671, No. 2, 1995, pp. 293-298.
M. P. Lambert, G. Stevens, S. Sabo, K. Barber, G. Wang, W. Wade, G. Krafft, S. Snyder, T. F. Holzman and W. L. Klein, “Beta/A4-evoked Degeneration of Differentiated SH-SY5Y Human Neuroblastoma Cells,” Journal Neuro- science Research, Vol. 39, No. 4, 1994, pp. 377-385.
A. Takashima, K. Noguchi, Satok, T. Hoshino and K. Imahori, “Tau Protein Kinase I Is Essential for Amyloid β-protein-induced Neurotoxicity,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 16, 1993, pp. 7789-7793.
G. E. Maestre, B. A. Tate, R. E. Majocha and C. A. Marotta, “Membrane Surface Ruffling in Cells That Over-express Alzheimer Amyloid β/A4 C-Terminal Peptide,” Brain Research, Vol. 62, 1993, pp. 145-149.
D. T. Loo, A. Copani, C. J. Pike, E. R. Whittemore, A. J. Walencewicz and C. W. Cotman, “Apoptosis is Induced by B-amyloid in Cultured Central Nervous System Neurons,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 17, 1993, pp. 7951-7955.
Y. Goodman and M. P. Mattson, “K+ Channel Openers Protect Hippocampal Neurons Against Oxidative Injury and Amyloid Beta-peptide Toxicity,” Brain Research, Vol. 706, No. 2, 1996, pp. 328-332.
I. N. Singh, G. Sorrentino and J. N. Kanfer, “Activation of LA-N-2 Cell Phospholipase D by Amyloid Beta Protein (25 - 35),” Neurochemical Research, Vol. 23, No. 10, 1998, pp. 1225-1232.
Y. Goodman, A. J. Bruce, B. Cheng and M. P. Mattson, “Estrogens Attenuate and Corticosterone Exacerbates Excitotoxicity, Oxidative Injury, and Amyloid Beta-Peptide Toxicity in Hippocampal Neurons,” Journal of Neuro- chemistry, Vol. 66, 1996, pp. 1836-1844.
H. Xu, G. K. Gouras, J. P. Greenfield, B. Vincent, J. Naslund, L. Mazzarelli, G. Fried, J. N. Jovanovic, M. Seeger, N. R. Relkin, F. Liao, F. Checler, J. D. Buxbaum, B. T. Chait, G. Thinakaran, S. S. Sisodia, R. Wang, P. Greengard and S. Gandy, “Estrogen Reduces Neuronal Generation of Alzheimer Beta-Amyloid Peptides,” Nature Medicine, Vol. 4, No. 4, 1998, pp. 447-451.
D. M. Araujo and C. W. Cotman, “Beta-Amyloid Sti- mulates Glial Cells in Vitro to Produce Growth Factors that Accumulate in Senile Plaques in Alzheimer’s Di- sease,” Brain Research, Vol. 569, 1992, pp. 141-145.
C. J. Pike, B. J. Cummings, R. Monzani and C. W. Cot- man, “β-Amyloid Induced Changes in Cultured Astrocytes Parallel Reactive Astrocytosis Associated With Senile Plaques in Alzheimer’s Disease,” Neuroscience, Vol. 63, No. 2, 1994, pp. 517-531.
L. Meda, M. A. Cassatella, G. I. Szendrei, L. Otvos Jr, P. Baron, M. Villalba, D. Ferrari and F. Rossi, “Activation of Microglial Cells by B-amyloid Protein and Interferon- γ,” Nature, Vol. 374, 1995, pp. 647-650.
A. Klegeris, D. G. Walker and P. L. McGeer, “Activation of Macrophages by Alzheimer B Amyloid Peptide,” Bio- chemical and Biophysical Research Communications, Vol. 199, 1994, pp. 984-991.
N. Arispe, E. Rojas and H. B. Pollard, “Alzheimer Disease Amyloid B Protein Forms Calcium Channels in Bilayer Membranes: Blockade by Tromethamine and Aluminium,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 2, 1993, pp. 567- 571.
R. M. Davidson, L. Shajenko and T. S. Donta, “Amyloid Beta-peptide (ABP) Potentiates a Nimodipine – Sensitive L-Type Barium Conductance in NIE-115 Neuroblastoma Cells,” Brain Research, Vol. 643, 1994, pp. 324-327.
P. Kuner, R. Schubenel and C. Hertel, “Beta-Amyloid Binds to p57NTR and Activates NF KappaB in Human Neuroblastoma Cells,” Journal of Neuroscience Research, Vol. 54, 1998, pp. 798-804.
T. Dyrks, E. Dyrks, U. Monning, B. Urmoneit, J. Turner and K. Beyreuther, “Generation of Beta A4 from the Amyloid Precursor and Fragments Thereof,” FEBS Letters, Vol. 335, 1993, pp. 89-93.
J. Ma, A. Yee, H. B. Brewer, S. Das and H. Potter, “Amyloid-Associated Proteins α, -Antichymotrypsin and Apolipoprotein ε Promote Assembly of Alzheimer B- Protein into Filaments,” Nature, Vol. 372, 1994, pp. 92- 94.
E. H. Corder, A. M. Saunders, W. J. Strittmatter, D. E. Schmechel, P. C. Gaskell, G. W. Small, A. D. Roses, J. L. Haines and M. A. Pericak-Vance, “Gene Dose of Apoli- poprotein E Type 4 Allele and the Risk of Alzheimer’s Disease in Late Onset Families,” Science, Vol. 261, No. 5123, 1993, pp. 921-923.
W. J. Strittmatter, A. M. Saunders, D. Schmechel, M. Pericak-Vance, J. Enghild, G. S. Salvesen and A. D. Roses, “Apolipoprotein E4 High Avidity Binding to β-amyloid and Increased Frequency of Type 4 Allele in Late-Onset Familial Alzheimer’s Disease,” Proceedings of the Na- tional Academy of Sciences of the United States of America, Vol. 90, 1993, pp. 1977-1981.
H. Hartmann, A. Eckert and W. E. Muller, “Apoli- poprotein E and Cholesterol Affect Neuronal Calcium Signalling: The Possible Relationship to Beta- amyloid Neurotoxicity,” Biochemical and Biophysical Research Communications, Vol. 200, No. 3, 1994, pp. 1185- 1192.
Y. H. Chong and Y. H. Suh, “Aggregation of Amyloid Precursor Proteins by Aluminium in Vitro,” Brain Re- search, Vol. 670, 1995, pp. 137-141.
G. D. Fasman, A. Perczel and C. D. Moore, “Solubilization of β-Amyloid-(1-42)-Peptide: Reversing the B-shed Con- formation Induced by Aluminium with Silicates,” Pro- ceedings of the National Academy of Sciences of the United States of America, Vol. 92, 1995, pp. 369- 371.
T. Dyrks, E. Dyrks, T. Hartmann, C. Masters and K. Beyreuther, “Amyloidogenicity of Beta A4 and Beta A4- bearing Amyloid Protein Precursor Fragments By Metal- catalyzed Oxidation,” Journal of Biological Chemistry, Vol. 267, No. 25, 1992, pp. 18210-18217.
P. W. Mantyh, J. R. Ghilardi, S. Rogers, E. DeMaster, C. J. Allen, E. R. Stimson and J. E. Maggio, “Aluminium, Iron and Zinc Ions Promote Aggregation of Physiological Concentrations of Beta-amyloid Peptide,” Journal of Neurochemistry, Vol. 61, No. 3, 1993, pp. 1171-1174.
H. LeVine 3rd, “Thioflavine T Interaction with Synthetic Alzheimer’s Disease Beta-Amyloid Peptides: Detection of Amyloid Aggregation in Solution,” Protein Science, Vol. 2, 1993, pp. 404-410.
H. LeVine 3rd, “Stopped-Flow Kinetics Reveal Multiple Phases of Thioflavin T Binding to Alzheimer Beta (1 - 40) Amyloid Fibrils,” Archives of Biochemistry and Biophy- sics, Vol. 342, No. 2, 1997, pp. 306-316.
A. Lorenzo and B. A. Yankner, “β-Amyloid Neuro- toxicity Requires Fibril Formation and Is Inhibited by Congo Red,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 2, 1994, pp. 12243-12247.
P. H. Jensen, E. S. Sorensen, T. E. Petersen, J. Gliemann and L. K. Rasmussen, “Residues in the Synuclein Con- sensus Motif of the Alpha-Synuclein Fragment, NAC, Participate in Translgutaminase-catalysed Cross-Linking to Alzheimer-Disease Amyloid Beta A4 Peptide,” Bio- chemical Journal, Vol. 310, 1995, pp. 91-94.
S. R. Paik, J. H. Lee, D. H. Kim, C. S. Chang and Y. S. Kim, “Self-Oligomerization of NACP, the Precursor Protein of the Non-Amyloid Beta/A4 Protein (A Beta) Component of Alzheimer’s Disease Amyloid, Observed in the Presence of a C-Terminal A Beta Fragment (Re- sidues 25 - 35),” FEBS Letters, Vol. 42, 1998, pp. 73-76.
M. Mullan, F. Crawford, K. Axelman, H. Houlden, L. Lilius, B. Winblad and L. Lannfelt, “A Pathogenic Mutation for Probable Alzheimer’s Disease in the APP Gene at the N-Terminus of β-Amyloid,” Nature Ge- netics, Vol. 1, 1992, pp. 345-347. doi:10.1038/ng0892-345
Q. Guo, K. Furukawa, B. L. Sopher, D. G. Pham, J. Xie, N. Robinson, G. M. Martin and M. P. Mattson, “Alzheimer’s PS-1 Mutation Perturbs Calcium Homeo-Stasis and Sensitizes PC12 Cells to Death Induced by Amy- loid Beta-Peptide,” NeuroReport, Vol. 8, 1996, pp. 379-383.
M. Bigl and K. Eschrich, “Interaction of Rat Brain Phosphofructokinase with Alzheimer’s Beta A4 Amy- loid,” Neurochemistry International, Vol. 26, No. 1, 1995, pp. 69-75.
J. I. Nagy, M. Z. Hossain, E. L. Hertzberg and C. A. Marotta, “Induction of Connexin43 and Gap Junctional Communication in PC12 Cells Overexpressing the Carboxy Terminal Region of Amyloid Precursor Protein,” Journal of Neuroscience Research, Vol. 44, No. 2, 1996, pp. 124-132.
S. D. Yan, X. Chen, J. Fu, M. Chen, H. Zhu, A. Roher, T. Slattery, L. Zhao, M. Nagashima, J. Morser, A. Migheli, P. Nawroth, D. Stern and A. M. Schmidt, “Rage and Amyloid-β Peptide Neurotoxicity in Alzheimer’s Di- sease,” Nature, Vol. 382, No. 6593, 1996, pp. 685-691.
S. D. Yan, J. Fu, C. Soto, X. Chen, H. Zhu, F. Al- Mohanna, K. Collison, A. Zhu, E. Stern, T. Saido, M. Tohyama, S. Ogawa, A. Roher and D. Stern, “An Intracellular Protein that Binds Amyloid-β Peptide and Mediates Neuro- toxicity in Alzheimer’s Disease,” Nature, Vol. 389, No. 6652, 1997, pp. 689-695.
S. J. Soscia, J. E. Kirby, K. J. Washicosky, S. M. Tucker, M. Ingelsson, B. Hayman, M. A. Burton, L. E. Goldstein, S. Duong, R. E. Tanzi and R. D. Moir, “The Alzheimer’s Disease-Associated Amyloid β-Protein Is an Anti- microbial Peptide,” Plos One, Vol. 5, No. 3, 2010, pp. e9505.
F. Kamenetz, T. Tomita, H. Hsieh, G. Seabrook, D. Borchelt, T. Iwatsubo, S. Sisodia and R. Malinow, “APP Processing and Synaptic Function,” Neuron, Vol. 37, No. 6, 2003, pp. 925-937.
S. Lesne, C. Ali, C. Garbiel, N. Croci, E. T. MacKenzie, C. G. Glabe et al., “NMDA Receptor Activation Inhibits Alpha-Secretase and Promotes Neuronal Amyloid-beta Production,” Journal of Neuroscience, Vol. 25, No. 41, 2005, pp. 9367-9377. doi:10.1523/JNEUROSCI.0849-05.2005
J. P. Steinbach, U. Muller, M. Leist, Z. W. Li, P. Nicotera and A. Aguzzi, “Hypersensitivity to Seizures in Beta- amyloid Precursor Protein Deficient Mice,” Cell Death and Differentiation, Vol. 5, No. 10, 1998, pp. 858-866.
H. Y. Wang, D. H. S. Lee, M. R. D’Andrea, P. A. Peterson, R. P. Shank and A. B. Reitz, “β-amyloid1-42 Binds to α7 Nicotinic Acetylcholine Receptor with High Affinity. Im- plications for Alzheimer’s Disease Pathology,” Journal of Biological Chemistry, Vol. 275, 2000, pp. 5626-5632.
H. Y. Wang, D. H. S. Lee, C. B. Davis and P. Shank, “Aβ1-42 Binds Selectively and with Picomolar Affinity to a7 Nicotinic Acetylcholine Receptors,” Journal of Neuro- chemistry, Vol. 75, 2000, pp. 1155-1161.
J. M. McDonald, G. M. Savva, C. Brayne, A. T. Welzell, G. Forster, G. M. Shankar, D. J. Selkoe, P. G. Ince and D. M. Walsh, “The Presence of Sodium Dodecyll Sulphate- stable A Dimmers Is Strongly Associated with Alzhei- mer-Type Dementia,” Brain, Vol. 133, 2010, pp. 1328- 1341.
M. Townsend, G. M. Shankar, T. Mehta, D. M. Walsh and D. J. Selkoe, “Effects of Secreted Oligomers of Amyloid β-Protein on Hippocompal Synaptic Plasticity: A Potent Role for Trimers,” Journal of Physiology, Vol. 572, No. 2, 2005, pp. 4767-492.
D. M. Walsh, I. Klyubin, J. V. Fadeeva, W. K. Cullen, R. Anwyl, M. S. Wolfe, M. J. Rowan and D. J. Selkoe, “Naturally Secreted Oligomers of Amyloid β Protein Potently Inhibit Hippocampal Long-Term Potentiation in Vivo,” Nature, Vol. 416, No. 6880, 2002, pp. 535-539.
D. J. Selkoe, “Soluble Oligomers of the Amyloid Beta- Protein Impair Synaptic Plasticity and Behaviour,” Be- havioural Brain Research, Vol. 28, 2008, pp. 106-113.
H. Hsieh, J. Boehm, C. Sato, T. Iwatsubo, T. Tomita, S. Sisodia, et al. “AMPAR Removal Underlies Abeta-In- duced Synaptic Depression and Dendritic Spine Loss,” Neuron, Vol. 52, No. 5, 2006, pp. 831-843.
G. M. Shanker, B. L. Bloodgood, M. Townsend, et al. “Natural Oligomers of the Alzheimer Amyloid-beta Protein Induce Reversible Synapse Loss of Modulating an NMDA-Type Glutamate Receptor-Dependent Signaling Pathway,” Journal of Neuroscience, Vol. 27, 2007, pp. 2866-2875.
T. Tomiyama, S. Matsuytama, H. Iso, T. Umeda, H. Takuma, K. Ohnishi, K. Ishibashi, R. Teraoka, N. Sakama, T. Yamashita, K. Nishitsuji, K. Ito, H. Shimada, M. P. Lambert, W. L. Klein and H. Mori, “A Mouse Model of Amyloid β Oligomers: Their Contribution to Synaptic Alteration, Abnormal Tau Phosphorylation, Glial Acti- vation and Neuronal Loss in Vivo,” Journal of Neuro- science, Vol. 30, No. 14, 2010, pp. 4845-4856.
S. A. Funker, T. van Groen, I. Kadish, D. Bartnik, L. Nagel-Steger, O. Brener, T. Sehl, B. Batra-Saffering, C. Moriscot, G. Schoehn, A. H. C. Horn, A. Maller- Schiffmann, C. Korth, H. Sticht and D. Willbold, “Oral Treatment with the D-Enantiomeric Peptide D3 Improves the Pathology and Behaviour of Alzheimer’s Disease Transgenic Mice,” ACS Chemical Neuroscience, Vol. 1, 2010, pp. 639-648.
S. Salloway, R. Sperling, S. Gilman, et al. “A Phase 2 Multiple Ascending Dose Trial of Bapineuzumab in Mild to Moderate Alzheimer Disease,” Neurology, Vol. 73, No. 24, 2009, pp. 2061-2070.
J. J. O. Rinne, D. J. Brooks, M. N. Rossor, N. C. Fox, R. Bullock, W. E. Klunk, C. A. Mathis, K. Blennow, J. Barakos, A. A. Okello, S. R. M. de Llano, E. Liu, M. Koller, K. M. Gregg, D. Schenk, R. Black and M. Grund- man, “11C-PiB PET Assessment of Change in Fibrillar Amyloid-b Load in Patients with Alzheimer’s Disease Treated with Bapineuzumab: A Phase 2, Double- blind, Placebo-Controlled, Ascending-Dose Study,” Lancet Neu- rology, Vol. 9, 2010, pp. 363-372.
J. Cleary, J. M. Hittner, M. Semotuk, P. Mantyh and E. O’Hare, “Beta-Amyloid (1 - 40) Effects on Behaviour and Memory,” Brain Research, Vol. 682, 1995, pp. 69-74. doi:10.1016/0006-8993(95)00323-I
D. L. Sparks, “Intraneuronal Beta-amyloid Immunoreacti- vity in the CNS,” Neurobiology of Aging, Vol. 17, No. 2, 1996, pp. 291-299.
W. A. Sweeney, J. Luedtke, M. P. McDonald and J. B. Overmier, “Intrahippocampal Injections of Exogenous Beta-amyloid Induce Postdelay Errors in an Eight-arm Radial Maze,” Neurobiology of Learning and Memory, Vol. 68, No. 1, 1997, pp. 97-101.
G. Jansco, F. Domoki, P. Santha, J. Varga, J. Fischer, K. Orosz, B. Penke, A. Becskei, M. Dux and L. Toth, “B- amyloid (1 - 42) Peptide Impairs Blood-brain Barrier Function After Intracarotid Infusion in Rats,” Neuroscien- ce Letters, Vol. 253, 1998, pp. 139-141.
G. C. Su, G. W. Arendash, R. N. Kalaria, K. B. Bjugstad and M. Mullan, “Intravascular Infusions of Soluble B- amyloid Compromise Blood-brain Barrier, Activate CNS Glial Cells and Induce Peripheral Hemorrhage,” Brain Research, Vol. 818, 1999, pp. 105-117.
J. Mackic, M. Weiss, W. Mhao, E. Kirkman, J. Ghiso, M. Calero, J. Bading, B. Frangione and B. V. Zlokovic, “Cerebrovascular Accumulation and Increased Blood- brain Barrier Permeability to Circulating Alzheimer’s Amyloid Beta Peptide in Aged Squirrel Monkey and Cerebral Amyloid Angiopathy,” Journal of Neurochemis- try, Vol. 70, 1998, pp. 210-215.
J. F. Flood, E. Roberts, M. A. Sherman, B. E. Kaplan and J. E. Morley, “Topography of a Binding Site for Small Amnestic Peptides Deduced from Structure-activity Studies: Relation to Amnestic Effect of Amyloid B Protein,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, 1994, pp. 380-384.
H. Komano, M. Seeger, S. Gandy, G. T. Wang, G. A. Krafft and R. S. Fuller, “Involvement of Cell Surface Glycosyl-Phosphatidylinositol-Linked Aspartyl Proteases in Alpha-Secretase-Type Cleavage and Ectodomain Solu- bilization of Human Alzheimer Beta-amyloid Precursor Protein in Yeast,” Journal of Biological Chemistry, Vol. 273, No. 48, 1998, pp. 31648-31651.
R. L. Neve, A. Kammesheidt and C. F. Hohmann, “Brain Transplants of Cells Expressing the Carboxyl-terminal Fragment of the Alzheimer Amyloid Protein Precursor Cause Neuropathology in Vivo,” Proceedings of the Na- tional Academy of Sciences of the United States of America, Vol. 89, 1992, pp. 3448-3452.
B. Tate, K. S. Aboody-Guterman, A. M. Morris, E. C. Walcott, R. E. Majocha and C. A. Marotta, “Disruption of Circadian Regulation by Brain Grafts that Overexpress Alzheimer Beta/A4 Amyloid,” Proceedings of the Na- tional Academy of Sciences of the United States of America, Vol. 89, No. 15, 1992, pp. 7090-7094.
R. E. Tanzi, J. F. Gusella, P. C. Watkins, G. A. Bruns, P. St George-Hyslop, M. L. Van Keuren, D. Patterson, S. Pagan, D. M. Kurnit and R. L. Neve, “Amyloid Beta Protein Gene: cDNA, mRNA Distribution, and Genetic Linkage Near the Alzheimer Locus,” Science, Vol. 235, No. 4791, 1987, pp. 880-884.
D. K. Lahiri and N. K. Robakis, “The Promoter Activity of the Gene Encoding Alzheimer B-amyloid Precursor Protein (APP) is Regulated by Two Blocks of Upstream Sequences,” Molecular Brain Research, Vol. 9, No. 3, 1991, pp. 253-257.
W. J. Lukiw, E. I. Rogaev, L. Wong, G. Vaula, D. R. C. McLachlan and P. St George Hyslop, “Protein-DNA Inter- actions in the Promoter Region of the Amyloid Precursor Protein (APP) Gene in Human Neocortex,” Molecular Brain Research, Vol. 22, No. 1-4, 1994, pp. 121-131.
J. M. Salbaum, A. Weidemann, H. G. Lemaire, C. L. Masters and K. Beyreuther, “The Promoter of Alzheimer’s Disease Amyloid A4 Precursor Gene,” EMBO Journal, Vol. 7, No. 9, 1988, pp. 2807-2813.
K. Beyreuther, P. Pollwein, G. Multhaup, U. Monning, G. Konig, T. Dyrks, W. Schubert and C. L. Masters, “Re- gulation and Expression of the Alzheimer’s β/A4 Amyloid Protein Precursor in Health, Disease, and Down’s Syn- drome,” Annals of the New York Academy of Science, Vol. 695, 1993, pp. 91-102.
R. Adroer, C. Lopez-Acedo and R. Oliva, “Conserved Elements in the 5’ Regulatory Region of the Amyloid Precursor Protein Gene in Primates,” Neuroscience Letters, Vol. 226, No. 3, 1997, pp. 203-206.
S. Silhol, A. Calenda, V. Jallageas, N. Mestre-Frances, M. Bellis and N. Bons, “Beta-Amyloid Protein Precursor in Microcebus Murinus: Genotyping and Brain Localiza- tion,” Neurobiology of Disease, Vol. 3, No. 3, 1996, pp. 169-182.
F. W. van Leeuwen, D. P. de Kleijn, H. H. van den Hurk, A. Neubauer, M. A. F. Sonnemans, J. A. Sluijs, S. Koycu, R. D. J. Ramdjielal, A. Salehi, G. J. M. Martens, F. G. Grosveld, J. P. H. Burbach and E. M. Hol, “Frameshift Mutants of Beta Amyloid Precursor Protein and Ubiquitin- B in Alzheimer’s and Down Patients,” Science, Vol. 279, No. 5348, 1998, pp. 242-247.
H. Reznik-Wolf, J. Machado, V. Haroutunian, L. DeMarco, G. F. Walter, B. Goldman, M. Davidson, J. A. Johnston, L. Lannfelt, S. U. Dani and E. Friedman, “Somatic Mutation Analysis of the APP and Presenilin 1 and 2 Genes in Alzheimer’s Disease Brains,” Journal of Neurogenetics, Vol. 12, No. 1, 1998, pp. 55-65.
Y. Arai, A. Suzuki, M. Mizuguchi and S. Takashima, “Developmental and Aging Changes in the Expression of Amyloid Precursor Protein in Down Syndrome Brains,” Brain and Development, Vol. 19, No. 4, 1997, pp. 290- 294.
B. Rumble, R. Retallack, C. Hilbich, G. Simms, G. Multhaup, R. Martins, A. Hockey, P. Montgomery, K. Beyreuther and C. L. Masters, “Amyloid A4 Protein and its Precursor in Down’s Syndrome and Alzheimer’s Disease,” New England Journal of Medicine, Vol. 320, No. 22, 1989, pp. 1446-1452.
J. K. Teller, C. Russo, L. M. DeBusk, G. Angelini, D. Zaccheo, F. Dagna-Bricarelli, P. Scartezzini, S. Bertolini, D. M. Mann, M. Tabaton and P. Gambetti, “Presence of Soluble Amyloid Beta-peptide Precedes Amyloid Plaque Formation in Down’s Syndrome,” Nature Medicine, Vol. 2, No. 1, 1996, pp. 93-95.
Q. X. Li, G. Evin, D. H. Small, G. Multhaup, K. Beyreuther and C. L. Masters, “Proteolytic Processing of Alzheimer’s Disease Beta A4 Amyloid Precursor Protein in Human Platelets,” Journal of Biological Chemistry, Vol. 270, No. 23, 1995, pp. 14140-14147.
P. Buckland, S. Tidmarsh, G. Spurlock, F. Kaiser, M. Yates, G. O’Mahony and P. McGuffin, “Amyloid Pre- cursor Protein mRNA Levels in the Mononuclear Blood Cells of Alzheimer’s and Down’s Patients,” Molecular Brain Research, Vol. 18, No. 4, 1993, pp. 316-320.
S. Ledoux, C. Bergeron, J. Nalbantoglu, S. Gauthier and N. R. Cashman, “Polymerase Chain Reaction Quantifica- tion of Lymphoid Amyloid Precursor Protein mRNAs in Alzheimer’s Disease and Down’s Syndrome,” Neurosci- ence Letters, Vol. 193, No. 2, 1995, pp. 137-139.
F. Kametani, K. Tanaka, T. Tokuda and S. Ikeda, “Secretory Cleavage Site of Alzheimer Amyloid Pre- cursor Protein is Heterogeneous in Down’s Syndrome Brain,” FEBS Letters, Vol. 351, No. 2, 1994, pp. 165- 167.
S. Govoni, S. Bergamaschi, L. Gasparini, C. Quaglia, M. Racchi, E. Cattaneo, G. Binetti, A. Bianchetti, F. Giovetti, F. Battaini and M. Trabuechi, “Fibroblasts of Patients Affected by Down’s Syndrome Oversecrete Amyloid Precursor Protein and are Hyporesponsive to Protein Kinase C Stimulation,” Neurology, Vol. 47, No. 4, 1996, pp. 1069-1075.
K. Urakami, J. Kataoka, A. Okada, K. Isoe, Y. Wakutani, Y. Ji, Y. Adachi, K. Ohno and K. Takahashi, “Analysis of Amyloid Precursor Protein mRNAs in Skin Fibroblasts in Down’s Syndrome,” Dementia, Vol. 7, No. 2, 1996, pp. 82-85.
C. Pallister, S. S. Jung, I. Shaw, J. Nalbantoglu, S. Gauthier and N. R. Cashman, “Lymphocyte Content of Amyloid Precursor Protein is Increased in Down’s Syndrome and Aging,” Neurobiology of Aging, Vol. 18, No. 1, 1997, pp. 97- 103. doi:10.1016/S0197-4580(96)00207-2
A. Goate, M. C. Chartier-Harlin, M. Mullan, J. Brown, F. Crawford, L. Fidani, L. Giuffra, A. Haynes, N. Irving and L. James, “Segregation of a Missense Mutation in the Amyloid Precursor Protein Gene with Familial Alzheimer’s Disease,” Nature, Vol. 349, No. 6311, 1991, pp. 704-706.
M. C. Chartier-Harlin, J. Hardy and M. Mullan, “Early Onset Alzheimer’s Disease Caused by Mutations at Codon 717 of the β-amyloid Precursor Protein Gene,” Nature, Vol. 353, 1991, pp. 844-846.
X. D. Cai, T. E. Golde and S. G. Younkin, “Excess Amyloid Beta-Protein is Released from a Mutant Amyloid Beta Protein Precursor Linked to Familial Alzheimer’s Disease,” Science, Vol. 259, 1993, pp. 514-516.
M. Citron, T. Olterdorf, C. Haass, L. McConlogue, A. Y. Hung, P. Seubert, C. Vigo-Pelfrey, I. Lieberburg and D. J. Selkoe, “Mutation of the Beta-Amyloid Precursor Protein in Familial Alzheimer’s Disease Causes Increased Beta Amyloid Production,” Nature, Vol. 360, 1992, pp. 672- 674.
L. Hendricks, C. M. van Duijn, P. Cras, M. Cruts, W. Van Hul, F. van Harskamp, A. Warren, M. G. McInnis, S. E. Antonarakis and J. J. Martin, “Presenile Dementia and Cerebral Haemorrhage Linked to a Mutation at Codon 692 of the β-amyloid Precursor Protein Gene,” Nature Genetics, Vol. 1, 1992, pp. 218-221.
C. Van Broeckhaven, J. Haan, E. Bakker, J. A. Hardy, W. Van Hul, A. Wehnert, M. Vegter-Van der Vlis and R. A. Roos, “Amyloid β Protein Precursor Gene and Hereditary Cerebral Haemorrhage with Amyloidosis (Dutch),” Science, Vol. 248, No. 4959, 1990, pp. 1120-1122.
E. Levy, M. D. Cumon, I. J. Fernandez-Madrid, M. D. Power, I. Lieberburg, S. G. van Duinen, G. T. Bots, W. Luyendijk and B. Frangione, “Mutation of the Alzhei- mer’s Disease Amyloid Gene in Hereditary Cerebral Haemorrhage, Dutch Type,” Science, Vol. 248, 1990, pp. 1124-1126.
P. K. Panegyres, J. Kwok, P. Schofield and P. C. Blumbergs, “A Western Australian Kindred with Dutch Cerebral Amyloid Angiopathy,” Journal of Neurological Sciences, Vol. 239, No. 1, 2005, pp. 75-80.
M. Simons, P. J. Tienari, C. G. Dotti and K. Beyreuther, “Two-Dimensional Gel Mapping of the Processing of the Human Amyloid Precursor Protein in Rat Hippocampal Neurons,” FEBS Letters, Vol. 368, No. 2, 1995, pp. 363- 366.
A. Marutle, U. Warpman, N. Bogdanovic, L. Lannfelt and A. Nordberg, “Neuronal Nicotinic Receptor Deficits in Alzheimer Patients with the Swedish Amyloid Precursor Protein 670/671 Mutation,” Journal of Neurochemistry, Vol. 72, No. 3, 1999, pp. 1161-1169.
E. Levy-Lahad, E. M. Wijsman, E. Nemens, I. Anderson, K. A. B. Goddard, J. L. Weber, T. D. Bird and G. D. Schellenberg, “A Familial Alzheimer’s Disease Locus on Chromosome 1,” Science, Vol. 269, No. 5226, 1995, pp. 970-973.
R. Sherrington, E. I. Rogaev, Y. Liang, E. A. Rogaeva, G. Levesque, M. Ikeda, H. Chi, C. Lin, G. Li and K. Holman, “Cloning of a Gene Bearing Missense Mutations in Early Onset Familial Alzheimer’s Disease,” Nature, Vol. 375, 1995, pp. 754-760.
D. Blacker and R. E. Tanzi, “The Genetics of Alzheimer Disease,” Archives of Neurology, Vol. 55, 1998, pp. 294- 296.
H. W. Querfurth, E. M. Wijsman, P. H. St George-Hislop and D. J. Selkoe, “βAPP mRNA Transcription is In- creased in Cultured Fibroblasts from the Familial Alzh- eimer’s Disease-1 Family,” Molecular Brain Research, Vol. 28, 1995, pp. 319-337.
D. R. Borchelt, G. Thinakaran, C. B. Eckman, M. K. Lee, F. Davenport, T. Ratovitsky, C. M. Prada, G. Kim, S. Seekins, D. Yager, H. H. Slunt, R. Wang, M. Seeger, A. I. Levey, S. E. Gandy, N. G. Copeland, N. A. Jenkins, D. L. Price, S. G. Younkin and S. S. Sisodia, “Familial Alzhei- mer’s Disease-linked Presenilin 1 Variants Elevate Abeta1-42/1-40 Ratio in Vitro and in Vivo,” Neuron, Vol. 17, No. 5, 1996, pp. 1005-1013.
N. D. Mehta, L. M. Refolo, C. Eckman, S. Sanders, D. Yager, J. Perez-Tur, S. Younkin, K. Duff, J. Hardy and M. Hutton, “Increased Abeta42(43) from Cell Lines Express- ing Presenilin 1 Mutations,” Annals of Neurology, Vol. 43, No. 2, 1998, pp. 256-258. doi:10.1002/ana.410430217
M. Hutton and J. Hardy, “The Presenilins and Alzheimer’s Disease,” Human Molecular Genetics, Vol. 6, No. 10, 1997, pp. 1639-1646.
B. De Strooper, P. Saftig, K. Craessaerts, H. Van- derstichele, G. Guhde, W. Annaert, K. Von Figura and F. Van Leuven, “Deficiency of Presenilin-1 Inhibits the Nor- mal Cleavage of Amyloid Precursor Protein,” Nature, Vol. 391, No. 6665, 1998, pp. 387-390.
C. De Jonghe, C. Zehr, D. Yager, C. M. Prada, S. Younkin, L. Hendriks, C. Van Broeckhoven and C. B. Eckman, “Flemish and Dutch Mutations in Amyloid Beta Pre- cursor Protein Have Different Effects on Amyloid Beta Secretion,” Neurobiology of Disease, Vol. 5, No. 4, 1998, pp. 281-286.
D. M. Mann, T. Iwatsubo, N. J. Cairns, P. L. Lantos, D. Nochlin, S. M. Sumi, T. D. Bird, P. Poorkaj, J. Hardy, M. Hutton, G. Prihar, R. Crook, M. N. Rosso and M. Haltia, “Amyloid Beta Protein (Abeta) Deposition in Chro- mosome 14-linked Alzheimer’s Disease: Predomi- nance of Abeta42(43),” Annals of Neurology, Vol. 40, 1996, pp. 149-156.
D. M. Mann, T. Iwatsubo, Y. Ihara, N. J. Cairns, P. L. Lantos, N. Bogdanovic, L. Lannfelt, B. Winblad, M. L. Maat-Schieman and M. N. Rossor, “Predominant De- position of Amyloid-Beta 42(43) in Plaques in Cases of Alzheimer’s Disease and Hereditary Cerebral He- morrhage Associated with Mutations in the Amyloid Pre- cursor Protein Gene,” American Journal of Pathology, Vol. 148, 1996, pp. 1257-1266.
U. Giambarella, T. Yamatsuji, T. Okamoto, T. Matsui, T. Ikezu, Y. Murayama, M. A. Levine, A. Katz, N. Gautam and I. Nishimoto, “G Protein Betagamma Complex- mediated Apoptosis by Familial Alzheimer’s Disease Mutant of APP,” EMBO Journal, Vol. 16, No. 16, 1997, pp. 4897-4907.
R. D. Hollister, W. Kisiel and B. T. Hyman, “Immuno- histochemical Localization of Tissue Factor Pathway Inhibitor-1 (TFPI-1), a Kunitz Proteinase Inhibitor, in Alzheimer’s Disease,” Brain Research, Vol. 728, 1996, pp. 13-19.
O. Almkvist, H. Basun, S. L. Wagner, B. A. Rowe, L. O. Wahlund and L. Lannfelt, “Cerebrospinal Fluid Levels of Alpha-Secretase-Cleaved Soluble Amyloid Precursor Pro- tein Mirror Cognition in a Swedish Family with Alzheimer Disease and a Gene Mutation,” Archives of Neurology, Vol. 54, 1997, pp. 641-644.
H. Tanaka, M. Araki and T. Masuzawa, “Reaction of Astrocytes in the Gerbil Hippocampus Following Transient Ischemia: Immunocytochemical Observations with Anti- bodies against Glial Fibrillary Acidic Protein, Glutamine Synthetase, and S-100 Protein,” Experimental Neurology, Vol. 116, No. 3, 1992, pp. 264-274.
S. Tanaka, S. Nakamura, J. Kimura and K. Ueda, “Age-Related Change in the Proportion of Amyloid Precursor Protein mRNAs in the Gray Matter of Cerebral Cortex,” Neuroscience Letters, Vol. 163, No. 1, 1993, pp. 19-21.
S. A. Johnson, T. McNeill, B. Cordell and C. E. Finch, “Relation of Neuronal APP-751/APP-695 mRNA Ratio and Neuritic Plaque Density in Alzheimer’s Disease,” Science, Vol. 248, No. 4957, 1990, pp. 854-857.
S. A. Johnson, G. M. Pasinetti, P. C. May, P. A. Ponte, B. Cordell and C. E. Finch, “Selective Reduction of mRNA for the B-amyloid Precursor Protein that Lacks a Kunitz- type Protease Inhibitor Motif in Cortex of Alzheimer’s Brains,” Experimental Neurology, Vol. 102, No. 2, 1988, pp. 264-268.
G. Konig, J. M. Salbaum, D. Wiestler, W. Lang, H. P. Schmitt, C. L. Master and K. Beyreuther, “Alternative Splicing of the β/A4 Amyloid Gene of Alzheimer’s Disease in Cortex of Control and Alzheimer’s Disease Patients,” Molecular Brain Research, Vol. 9, 1991, pp. 259-262.
A. Matsumoto and R. Matsumoto, “Familial Alzheimer’s Disease Cells Abnormally Accumulate Beta-Amyloid- Harbouring Peptides Preferentially in Cytosol but Not in Extracellular Fluid,” European Journal of Biochemistry, Vol. 225, No. 3, 1994, pp. 1055-1062. doi:10.1111/j.1432-1033.1994.1055b.x
C. A. Robinson, A. W. Clark, I. M. Parhad, T. S. Fung and S. S. Bou, “Gene Expression in Alzheimer Neocortex as a Function of Age and Pathologic Severity,” Neuro- biology of Aging, Vol. 15, No. 6, 1994, pp. 681-690.
M. T. Webster, P. T. Francis, A. W. Procter, G. C. Stratman, R. Doshi, D. M. A. Mann and D. M. Bowan, “Postmortem Brains Reveal Similar but Not Identical Amyloid Precursor Protein-Like Immunoreactivity in Alzheimer Compared with Other Dementias,” Brain Re- search, Vol. 644, No. 2, 1994, pp. 347-351.
B. T. Hyman, J. J. Wenniger and R. E. Tanzi, “No- nisotopic in Situ Hybridization of Amyloid Beta Protein Precursor in Alzheimer’s Disease: Expression in Neuro- fibrillary Tangle Bearing Neurons and in the Micro- environment Surrounding Senile Plaques,” Molecular Brain Research, Vol. 18, No. 3, 1993, pp. 253-258. doi:10.1016/0169-328X(93)90197-W
R. E. Tanzi, J. J. Wenniger and B. T. Hyman, “Cellular Specificity and Regional Distribution of Amyloid β? Protein Precursor Alternative Transcripts Are Unaltered in Alzheimer Hippocampal Formation,” Molecular Brain Research, Vol. 18, No. 3, 1993, pp. 246-252.
P. J. Harrison, A. J. L. Barton, A. W. Procter, D. M. Bowen and R. C. A. Pearson, “The Effects of Alzheimer's Disease, Other Dementias, and Premortem Course on B-amyloid Precursor Protein Messenger RNA in Frontal Cortex,” Journal of Neurochemistry, Vol. 62, 1994, pp. 635-644.
D. J. S. Sirinathsinghji, M. Rigby, R. P. Heavens, D. Smith, J. M. Fernandez, R. Schuligol and R. G. Hill, “Increased Messenger RNA Expression of the 695 and 751 Amino Acid Isoforms of the β-Amyloid Protein Pre- cursor in the Thalamus of 17-Year-Old Cynomolgus (Ma- caca Fascicularis) Monkeys,” Neuroscience, Vol. 65, No. 1, 1995, pp. 51-57.
F. M. Flood, R. F. Cowburn and J. A. Johnston, “Presenilin-1, Amyloid Precursor Protein and Amyloid Precursor-like Protein 2 mRNA Levels in Human Su- perior Frontal Cortex During Aging,” Neuroscience Letters, Vol. 235, No. 1-2, 1997, pp. 17-20.
S. S. Zhan, R. Sandbrink, K. Beyreuther and H. P. Schmitt, “APP with Kunitz Type Protease Inhibitor Domain (KPI) Correlates with Neuritic Plaque Density but Not with Cortical Synaptophysin Immunoreactivity in Alzheimer’s Disease and Non-Demented Aged Subjects: A Multi- factorial Analysis,” Clinical Neuropathology, Vol. 14, No. 3, 1995, pp. 142-149.
P. K. Panegyres, K. Zafiris-Toufexis and B. A. Kakulas, “Amyloid Precursor Protein Gene Isoforms in Alzheimer’s Disease and Other Neurodegenerative Disorders,” Journal of Neurological Sciences, Vol. 173, No. 2, 2000, pp. 81-92.
P. Preece, D. J. Virley, M. Costandi, R. Coombes, S. J. Moss, A. W. Mudge, E. Jazin and N. J. Cairns, “Amyloid Precursor Protein mRNA Levels in Alzheimer’s Disease Brain,” Molecular Brain Research, Vol. 122, No. 1, 2004, pp. 1-9.
E. Cochran, B. Bacci, Y. Chen, A. Patton, P. Gambetti and L. Antiho-Gambetti, “Amyloid Precursor Protein and Ubiquitin Immunoreactivity in Dystrophic Axons is Not Unique to Alzheimer’s Disease,” American Journal of Pathology, Vol. 139, No. 3, 1991, pp. 485-489.
G. W. Roberts, S. M. Gentleman, A. Lynch and D. I. Graham, “BA4 Amyloid Protein Deposition in Brain after Head Trauma,” Lancet, Vol. 338, 1991, pp. 1422-1423.
P. C. Blumbergs, G. Scott, J. Manavis, H. Wainwright, D. A. Simpson and A. J. McLean, “Staining of Amyloid Precursor Protein to Study Damage in Mild Head Injury,” Lancet, Vol. 344, 1994, pp. 1055-1056.
A. M. Gleckman, M. D. Bell, R. J. Evans and T. W. Smith, “Diffuse Axonal Injury in Infants with Nonacci- dental Craniocerebral Trauma: Enhanced Detection by Beta-amyloid Precursor Protein Immunohistochemical Staining,” Archives of Pathology and Laboratory Me- dicine, Vol. 123, 1999, pp. 146-151.
B. Koszyca, P. C. Blumbergs, J. Manavis, H. Wainwright, R. James, J. Gilbert, N. Jones and P. L. Reilly, “Widespread Axonal Injury in Gunshot Wounds to the Head Using Amyloid Precursor Protein as a Marker,” Journal of Neuro- trauma, Vol. 15, No. 9 1998, pp. 675- 683.
W. S. T. Griffin, J. G. Sheng, S. M. Gentleman, D. I. Graham, R. E. Mrak and G. W. Roberts, “Microglial Interleukin-1a Expression in Human Head Injury: Co- rrelations with Neuronal and Neuritic B-amyloid Precursor Protein Expression,” Neuroscience Letters, Vol. 176, 1994, pp. 133-136.
W. S. T. Griffin, L. C. Stanley, C. Ling, L. White, V. MacLeod, L. J. Perrot, C. L. White 3rd and C. Araoz, “Brain Interleukin 1 and S100 Immunoreactivity Are Elevated in Down Syndrome and Alzheimer Disease,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 86, 1989, pp. 7611-7615.
J. G. Sheng, F. A. Boop, R. E. Mrak and W. S. T. Griffin, “Increased Neuronal B-amyloid Precursor Protein Ex- pression in Human Temporal Lobe Epilepsy: Associa- tion with Interleukin-1a Immunoreactivity,” Journal of Neurochemistry, Vol. 62, 1994, pp. 1872-1879.
D. Goldgaber, H. W. Harris, T. Hla, T. Maciag, R. J. Donnelly, J. S. Jacobsen, M. P. Vitek and D. C. Gajdusek, “Interleukin 1 Regulates Synthesis of Amyloid B-protein Precursor mRNA in Human Endothelial Cells,” Pro- ceedings of the National Academy of Sciences of the United States of America, Vol. 86, No. 19, 1989, pp. 7606-7610.
M. Di Luca, L. Pastorino, A. Bianchetti, J. Perez, L. A. Vignolo, G. L. Lenzi, M. Trabucchi, F. Cattabeni and A. Padovani, “Differential Level of Platelet Amyloid Beta Precursor Protein Isoforms: An Early Marker for Alzheimer Disease,” Archives of Neurology, Vol. 55, No. 9, 1998, pp. 1195-1200.
A. Henry, Q. X. Li, D. Galatis, L. Hesse, G. Multhaup, K. Beyreuther, C. L. Masters and R. Cappai, “Inhibition of Platelet Activation by the Alzheimer’s Disease Amyloid Precursor Protein,” British Journal of Haematology, Vol. 103, No. 2, 1998, pp. 402-415.
M. C. Sugarman, T. R. Yamasaki, S. Oddo, J. C. Echegoyen, M. P. Murphy, T. E. Golde, M. Jannatipour, M. A. Leissring and F. M. Laferla, “Inclusion Body Myositis-like Phenotype Induced by Transgenic Overex- pression of B APP in Skeletal Muscle,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, 2002, pp. 6334-6339.
N. J. Scolding, F. Joseph, P. A. Kirby, I. Mazanti, F. Gray, J. Mikol, D. Ellison, D. A. Hilton, T. L. Williams, J. M. MacKenzie, J. H. Xuereb and S. Love, “Aβ-related Angiitis: Primary Angiitis of the Central Nervous System Associated with Cerebral Amyloid Angiopathy,” Brain, Vol. 128, No. 3, 2005, pp. 500-515.