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Complement cascade activation by neurofibrillary tangles

by Aileen Anderson

10 November 1998. The complement cascade is a complex inflammatory process that can mediate diverse functions, from targeting cells and cellular components for phagocytosis to membrane attack complex-mediated cell death. In this context, there are twenty or more individual proteins that participate in the complement cascade. Immunoreactivity for a wide variety of complement proteins, e.g. C1q and the terminal membrane attack complex (MAC or C5b-9), has been reported in association with both ß-amyloid plaques and neurofibrillary tangles (NFT) in AD brain. Previous work by several laboratories including that of Joseph Rogers and Andrea Tenner, has demonstrated that ß-amyloid 1-42 can activate complement and bind complement proteins including the C1q A chain. In a newer study, Rogers, et al., report that a purified fraction of isolated NFTs can also activate a complement response (abstract 502.10). Recombinant tau also activated terminal complement in a dose-dependent manner nearly as efficiently as synthetic Aß 1-42. Further, a fraction of isolated tau that formed fibrils, as compared to soluble recombinant tau, activated complement even more strongly. These data may suggest that both ß-amyloid plaques and NTFs could serve as chronic mediators of an inflammatory response in the AD brain.