Inflammation and cerebral amyloidosis are disconnected in an animal model of Alzheimer's disease.
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)].
Quinn
Joseph
J
Portland Veteran's Affairs Medical Center, and Department of Neurology, Oregon Health Sciences University, 97201, USA. quinnj@ohsu.edu
Montine
Thomas
T
Morrow
Jason
J
Woodward
William R
WR
Kulhanek
Doris
D
Eckenstein
Felix
F
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
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D008070:Lipopolysaccharides