|Budget Amount *help
¥3,300,000 (Direct Cost : ¥3,300,000)
Fiscal Year 2000 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1999 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1998 : ¥1,400,000 (Direct Cost : ¥1,400,000)
To investigate risk factors for formation of Alzheimer type neuropathological changes such as senile plaques (SP), neurofibrillary tangles (NFT), and cerebral amyloid angiopathy (CAA), we performed pathological, immunohistochemical, and molecular genetic studies in the elderly Japanese individuals including patients with Alzheimer disease (AD). The results were summarized as follows :
1) A polymorphism in the intron 8 of presenilin 1 gene was associated with CAA, but not with AD, SP, or NFT.
2) A polymorphism in the signal peptide of alpha 1-antichymotrypsin (ACT) was associated with CAA in AD brains, but not with AD, SP, or NFT.
3) A polymorphism (K variant) in butyrylcholinesterase gene was associated with SP and NFT, but not with AD and CAA.
4) Polymorphisms in alpha2-macroglobulin and paraoxonase genes were not associated with AD, SP, NFT, or CAA.
In addition, we developed an in vitro system in which dissolution of beta amyloid fibrils as well as fibril formation of beta peptide can be monitored. The system would be useful to identify factors which influence amyloid fibrillogenesis in the brain.