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Although secondary to the fundamental pathology caused by the presence of tangles and plaques, there is strong evidence that inflammation exacerbates the neuronal loss. In particular, AD lesions show evidence of self-attack by the complement system--a part of the immune system that normally functions to rid the body of invading pathogens. However, the lesions are devoid of significant T cell infiltration, a hallmark of an inflammatory immune response, and antibodies. We define this phenomenon as autotoxicity to distinguish it from classical autoimmunity, in which the body raises antibodies to normal endogenous macromolecules. Locally produced inflammatory mediators have also been identified in atherosclerotic plaques, along with evidence of complement self-attack. As was previously shown for heart attacks, epidemiological evidence indicates that extended use of nonsteroidal anti-inflammatory drugs (NSAIDs) results in a reduced risk of AD. NSAIDs inhibit the production of prostaglandin inflammatory mediators, but powerful new therapeutic agents might be developed by targeting more critical inflammatory mechanisms, especially the complement system.<\/jats:p>","DOI":"10.1126\/sageke.2002.29.re3","type":"journal-article","created":{"date-parts":[[2003,8,8]],"date-time":"2003-08-08T00:18:50Z","timestamp":1060301930000},"source":"Crossref","is-referenced-by-count":34,"title":["Innate Immunity, Local Inflammation, and Degenerative Disease"],"prefix":"10.1126","volume":"2002","author":[{"given":"Patrick L.","family":"McGeer","sequence":"first","affiliation":[{"name":"The authors are in the Kinsmen Laboratory of Neurological Research at the University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.(P.L.M.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith G.","family":"McGeer","sequence":"additional","affiliation":[{"name":"The authors are in the Kinsmen Laboratory of Neurological Research at the University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.(P.L.M.)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_1_2","first-page":"39","volume":"33","year":"1991","unstructured":"P. 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