| 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)
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| 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.
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