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Abstract
Beta-amyloid (Aβ) 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 Aβ is linked to cognitive deterioration, the mechanisms of degradation and clearance of Aβ are now being researched for use in AD therapy. We conducted an immunohistochemical study of the patterns of deposition of two Aβ subtypes (Aβ40 and Aβ42) and the distribution of the Aβ degrading enzyme neprilysin (NEP) in the brains of aged squirrel monkeys, a species known to develop CAA and SPs. Aβ 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 Aβ40 is deposited predominantly in the arterioles of the meninges and penetrates vertically into the cerebral cortex, whereas Aβ42 is deposited predominantly in the capillaries of the cerebral cortex. These distinct patterns of deposition of Aβ 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.
Keywords:
| Abbreviations | ||
| Aβ | = | beta-amyloid |
| SP | = | senile plaque |
| CAA | = | cerebral amyloid angiopathy |
| AD | = | Alzheimer's disease |
| NEP | = | Neprilysin |
| LOAD | = | late-onset AD |
| AβPP | = | Aβ precursor protein |
| Abbreviations | ||
| Aβ | = | beta-amyloid |
| SP | = | senile plaque |
| CAA | = | cerebral amyloid angiopathy |
| AD | = | Alzheimer's disease |
| NEP | = | Neprilysin |
| LOAD | = | late-onset AD |
| AβPP | = | Aβ precursor protein |
Acknowledgements
The authors thank Dr. Hiroyuki Nakayama and Dr. Kazuyuki Uchida of the Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Science, The University of Tokyo, and Dr. Shin-ichiro Nakamura of the Research Center for Animal Life Science, Shiga University of Medical Science, for their generous advice and donation of the antibodies used in this study.