| Project/Area Number |
01480281
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Psychiatric science
|
|---|
| Research Institution | SAPPORO MEDICAL UNIVERSITY |
|---|
Principal Investigator |
FUKATSU Ryo SAPPORO MEDICAL UNIVERSITY,SCHOOL OF MEDICINE,ASSOCIATE PROFESSOR, 医学部, 助教授 (10113614)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
FUJII Mitsuru SAPPORO MEDICAL UNIVERSITY,SCHOOL OF MEDICINE,ASSISTANT PROFESSOR, 医学部, 講師 (80199299)
TAKAHATA Naohiko SAPPORO MEDICAL UNIVERSITY,SCHOOL OF MEDICINE,PROFESSOR, 医学部, 教授 (20000987)
相沢 裕二 札幌医科大学, 医学部, 助手 (60202446)
|
|---|
| Project Period (FY) |
1989 – 1991
|
| Project Status |
Completed (Fiscal Year 1991)
|
| Budget Amount *help |
¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1991: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1990: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1989: ¥3,500,000 (Direct Cost: ¥3,500,000)
|
|---|
| Keywords | Alzheimer's disease / monoclonal antibody / amyloid deposition / NFT / amyloid beta protein / apoE / SP-40,40 / amyloid associated proteins / アルツハイマ-病 / アミロイド / Bー蛋白 / serum protein 40ー40 / 35kDa蛋白 / モノクロ-ナル抗体 / βー蛋白 / Alzheimer's disease / PHF / Amyloid / monoclonal antibody / βーprotein / amyloid precursor protein |
|---|
| Research Abstract |
Cerebral amyloid deposits of varying morphology, and neurofibrillary tangles (NFT) are major neuropathological characteristics in Alzheimer's disease (AD) affected brains.
1) Twelve monoclonal antibodies (mcAb's) against cerebral amyloid were established. The antigens recognized were determined to be Abeta, C3, and C4. we characterized proteinchemically the antigen four mcAb's and two mcAb's recognized to be apoE and SP-40,40. The antigens recognized with Two mcAb's remained unidentified.
2) Twenty two mcAb's against PHF were established. The reactive antigens were tau protein, neurofilaments, and ubiquitin. The antigens which the rest of mcAb's e recognized were unidentified.
3) Using these mcAb's, immunohistochemical study showed that apoE was found in almost all amyloid depositions studied, and that there was a spatial relation between apoE overproducing astrocytes and plaques. NFT were stained with polyclonal apoE Ab, but not with our mcAb's. Competitive ELISA and Western blot analysis combined with thrombolytic digestion of apoE indicated that our four mcAb's recognized the epitopes within 22 kDa amino-terminal domain of apoE,and there were at least two distinct epitopes of the amino-terminal domain in amyloid depositions. SP-40,40 is present in various morphologies of Abeta depositions to a lessor degree and in astrocytes which are also located close to these depositions in brains affected by AD,and SDAT.These studies suggest that the mechanisms underlying the expression and processing of apoE,and SP-40,40 may be an essential issue in the pathogenesis of AD.
|
