title: The possible role of complement activation in Alzheimer disease.
abstract: Molecular pathological studies of Alzheimer disease (AD) brain have revealed the presence of a spectrum of inflammatory mediators. Epidemiological studies have indicated that the use of anti-inflammatory agents, especially non-steroidal anti-inflammatory drugs (NSAIDs), results in a substantially reduced risk of contracting the disease. It is possible that well targeted anti-inflammatory agents will also be useful in treating established AD. Inhibitors of cyclooxygenase-2 have been unsuccessful in this regard, and traditional NSAIDs have produced mixed results. The complement system, which is strongly activated in AD brain, is an attractive target for therapeutic intervention, particularly through inhibition of the autodestructive action of the membrane attack complex. The complement system works in conjunction with activated microglia, which express high levels of complement receptors. Overactive microglia secrete many toxic materials. Inhibition of microglial activation is another potential therapeutic target.
authors.affiliation: Kinsmen Laboratory of Neurological Research, Dept of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, BC, V6T 1Z3, Vancouver, Canada. mcgeerpl@interchange.ub.ca
authors.forename: Patrick L
authors.initials: PL
authors.lastname: McGeer
authors.forename: Edith G
authors.initials: EG
authors.lastname: McGeer
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000276:immunology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D003167:Complement Activation / Q000187:drug effects / Q000276:immunology*; D003165:Complement System Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D017628:Microglia / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003165:Complement System Proteins