Distribution of neprilysin and deposit patterns of Abeta subtypes in the brains of aged squirrel monkeys (Saimiri sciureus).

Beta-amyloid (Abeta) is deposited in the parenchyma and blood vessel walls of the senescent brain, and forms lesions termed senile plaques (SPs) and cerebral amyloid angiopathy (CAA). Since in Alzheimer's disease (AD) excessive Abeta is linked to cognitive deterioration, the mechanisms of degradation and clearance of Abeta are now being researched for use in AD therapy. We conducted an immunohistochemical study of the patterns of deposition of two Abeta subtypes (Abeta40 and Abeta42) and the distribution of the Abeta degrading enzyme neprilysin (NEP) in the brains of aged squirrel monkeys, a species known to develop CAA and SPs. Abeta deposits were observed mainly in the cerebral cortex of five older monkeys, and were absent in monkeys under 12 years of age. NEP expression was observed in the caudate nucleus, putamen, globus pallidus, substantia nigra and the molecular layer of the dentate gyrus, and thus exhibited a distribution complementary to those of CAA and SPs in cerebral cortex and hippocampus. It is known that CAA is more prominent than SPs in squirrel monkey brains. However, we confirmed that Abeta40 is deposited predominantly in the arterioles of the meninges and penetrates vertically into the cerebral cortex, whereas Abeta42 is deposited predominantly in the capillaries of the cerebral cortex. These distinct patterns of deposition of Abeta subtypes are likely related to the difference in biochemical character of these two subtypes. We have demonstrated for the first time the distribution of NEP in the brain of a non-human primate, the squirrel monkey, which appears useful for research on AD treatment.