Inflammatory processes and antiinflammatory drugs in Alzheimer's disease: a current appraisal.
The study of risk factors and protective influences can yield clues to the pathogenesis of Alzheimer's disease (AD). Intervention on such factors can effect disease prevention or treatment while etiology remains unknown. Most known AD risk factors offer no prospect of prevention, but 14 of 15 relevant publications since 1987 suggest that the symptoms of AD are prevented or attenuated by antiinflammatory treatments. These findings are supported by numerous circumstantial findings suggesting a role for cytokines and acute phase reactants in the pathogenesis of AD. In particular, activated microglia and/or reactive astrocytes, found within or near all AD lesions, are thought to kill target cells by using either free radicals or the classical complement pathway. These mechanisms should be suppressed by glucocorticoids, but the available data suggest that nonsteroidal antiinflammatory drugs (NSAIDs) exert a stronger protective influence than steriods. NSAIDs (but not steroids) suppress the action of cyclooxygenases (COX), which catalyze synthesis of prostaglandins. The latter are intermediaries in the postsynaptic signal transduction cascade of cells with NMDA-type glutamate receptors. They may also potentiate glutamatergic transmission by inhibiting astrocytic reuptake of glutamate. Both mechanisms can potentiate excitotoxic cell death. Further work is needed to clarify whether steroids, NSAIDs, or both prevent or attenuate the symptoms of AD.
Program in Epidemiology of Dementia, Duke University Medical Center, Durham, NC 27710, USA.
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JC
Breitner
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology*; D013256:Steroids
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D013256:Steroids