The role of complement and activated microglia in the pathogenesis of Alzheimer's disease.
A variety of inflammatory mediators including complement activation products, protease inhibitors, and cytokines are colocalized with beta-amyloid (A beta) deposits in the Alzeimer's disease (AD) brain. Activation products of the early complement components C1, C4, and C3 are always found in neuritic plaques and to a lesser extent in varying numbers of diffuse plaques. In contrast to these findings, no immunohistochemical evidence was obtained for the presence of the late complement components C7 and C9 and the complement membrane attack complex in the neuropathological lesions in AD brains. The mRNA encoding the late complement components C7 and C9 appears to be hardly or not detectable. These findings indicate that in AD the complement system does not act as an inflammatory mediator through membrane attack complex formation, but through the actions of the early complement products. In this review we focus on the role of complement in the pathological amyloid cascade in AD. In our opinion, the early complement activation products play a crucial role as mediators between the A beta deposits and the inflammatory responses leading to neurotoxicity.
Graduate School Neurosciences Amsterdam, Research Institute Neurosciences Vrije Universiteit, Department of Psychiatry, Amsterdam, The Netherlands.
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Eikelenboom
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Veerhuis
D000544:Alzheimer Disease / Q000276:immunology / Q000473:pathology*; D001921:Brain / Q000473:pathology; D003165:Complement System Proteins / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008262:Macrophage Activation / Q000502:physiology*; D017628:Microglia / Q000502:physiology*
D003165:Complement System Proteins