title: Inflammation and cerebral amyloidosis are disconnected in an animal model of Alzheimer's disease.
abstract: The hypothesis that inflammation and beta amyloid deposition are causally linked in Alzheimer's disease (AD) was tested in a transgenic mouse model. Untreated beta amyloid plaque-bearing Tg2576 mice did not differ from wild type animals in brain levels of most inflammatory mediators. Indomethacin treatment suppressed brain levels of prostaglandins by 90%, but reduced hippocampal beta amyloid by only 20%, with no effect on cortical beta amyloid. The discordant effects on beta amyloid and cyclooxygenase (COX) suggest that these effects of nonsteroidal anti-inflammatory drugs (NSAIDs) are not causally linked. Further evidence against a causal relationship is seen in an unexpected trend to lower levels of beta amyloid after an inflammatory stimulus [lipopolysaccharide (LPS)].
authors.affiliation: Portland Veteran's Affairs Medical Center, and Department of Neurology, Oregon Health Sciences University, 97201, USA. quinnj@ohsu.edu
authors.forename: Joseph
authors.initials: J
authors.lastname: Quinn
authors.forename: Thomas
authors.initials: T
authors.lastname: Montine
authors.forename: Jason
authors.initials: J
authors.lastname: Morrow
authors.forename: William R
authors.initials: WR
authors.lastname: Woodward
authors.forename: Doris
authors.initials: D
authors.lastname: Kulhanek
authors.forename: Felix
authors.initials: F
authors.lastname: Eckenstein
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D000686:Amyloidosis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D008070:Lipopolysaccharides