[Analysis of the 80 kDa antigen in senile plaque amyloid]

Amyloid deposition is the major hallmark of Alzheimer's disease (AD). Beta/A4 protein is identified as the major component of amyloid in the brains of AD. But all the components of amyloid and the precise mechanism of amyloid formation are still unknown. To provide better understanding of amyloidogenesis in AD brain, we have established 12 monoclonal antibodies (mcAb's) which immunohistochemically reacted with amyloid or amyloid-related structures, and tried to characterize these mcAb's. The epitopes, which these mcAb's reacted with, have been studied, and 2 of these mcAb's (Az 172/4, Az 520/4) turned out to react with protein of 80 kDa in brain homogenate or normal human plasma (NHP). Reactive antigen was purified from NHP using PEG fractionation, and immunoaffinity column. Amino-terminus amino acid sequence analysis of purified antigen was performed, and the results showed that 80 kDa antigen was identical to SP-40, 40 (or clusterin). Immunohistochemical study revealed that various types of senile plaque and vascular amyloid were stained with the mcAb's. In addition, fibrous background structures were also stained in AD brain. But there were no positive structures in control brains. The above observations indicate that SP-40, 40 is expressed and deposited in AD brain. This protein is closely associated with amyloid deposition. SP-40, 40 seems to play an important role in pathogenesis of amyloid formation in AD.