THE ROLE OF COMPLEMENT AND ACTIVATED MICROGLIA IN THE PATHOGENESIS OFALZHEIMERS-DISEASE

A variety of inflammatory mediators including complement activation pr oducts, protease inhibitors, and cytokines are colocalized with beta-a myloid (A beta) deposits in the Alzheimer's disease (AD) brain. Activa tion products of the early complement components C1, C4, and C3 are al ways found in neuritic plaques and to a lesser extent in varying numbe rs of diffuse plaques. In contrast to these findings, no immunohistoch emical evidence was obtained for the presence of the late complement c omponents C7 and C9 and the complement membrane attack complex in the neuropathological lesions in AD brains. The mRNA encoding the late com plement components C7 and C9 appears to be hardly or not detectable. T hese findings indicate that in AD the complement system does not act a s an inflammatory meditor through membrane attack complex formation, b ut through the actions of the early complement products. In this revie w we focus on the role of complement in the pathological amyloid casca de in AD. In our opinion, the early complement activation products pla y a crucial role as mediators between the A beta deposits and the infl ammatory responses leading to neurotoxicity.