Aim: The abnormal accumulation, assembly and deposition of the amyloid β -protein (A β ) are prominent pathological features of patients with Alzheimer’s disease (AD) and related disorders. A number of factors in the brain can influence A β accumulation and associated pathologies. The aim of the present study was to determine the consequences of delet ing nitric oxide synthase (NOS) 3, the endothelial form of NOS, in Tg-5xFAD mice, a model of parenchymal AD-like amyloid pathology. Methods: Tg-5xFAD mice were bred with NOS3 - / - mice. Cohorts of Tg-5xFAD mice and bigenic Tg-5xFAD/NOS3 - / - mice were aged to six months followed by collection of the blood and brain tissues from the mice for biochemical and pathological analyses. Results: ELISA analyses show that the absence of NOS3 results in elevated levels of cerebral and plasma A β peptides in Tg-5xFAD mice. Immunohistochemical analyses show that the absence of NOS3 increased the amount of parenchymal A β deposition and fibrillar amyloid accumulation in Tg-5xFAD mice. The elevated levels of A β were not due to changes in the expression levels of transgene encoded human amyloid precursor protein (APP), endogenous β -secretase, or increased proteolytic processing of APP. Conclusions: The results from this study suggest that the loss of NOS3 activity enhances A β pathology in Tg-5xFAD mice. These findings are similar to previous studies of NOS2 deletion suggesting that reduced NOS activity and NO levels enhance amyloid-associated pathologies in human APP transgenic mice.
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