NONSTEROIDAL ANTIINFLAMMATORY DRUG-USE AND ALZHEIMER-TYPE PATHOLOGY IN AGING

Anti-inflammatory drugs have been suggested as a possible treatment fo r Alzheimer's disease (AD). The association of immune proteins and imm une-competent microglial cells with senile plaques (SP) in both AD and normal aging suggests that these drugs may be able to modify the cour se of AD, either by interfering with SP formation or by suppressing th e inflammation associated with SP. We compared postmortem brain tissue from elderly, nondemented, arthritic patients with a history of chron ic nonsteroidal anti-inflammatory drug (NSAID) use (n = 32, aged 77 +/ - 7 years) and nondemented control subjects with no history of arthrit is or other condition that might promote the regular use of NSAIDs (n = 34, aged 77 +/- 6 years). In both the NSAID-treated group and contro l subjects, 59% of patients had some SP. There was no difference betwe en the two groups in the mean number of plaques or in the number of sp ecific SP subtypes (diffuse or neuritic). The degree of neurofibrillar y pathology was also similar. Activated microglia were identified usin g CR3/43, an anti-MHC class II antibody. Both patient age and the pres ence of SP correlated positively with the number of CR3/43+ microglia (p < 0.02), whereas NSAID use was associated with less microglial acti vation (p < 0.01). Control patients with SP had almost three times the number of activated microglia as NSAID-treated patients with SP (11 v ersus 4 cells/mm(2), p < 0.02). These results suggest that if NSAID us e is effective in treating AD, the mechanism is more likely to be thro ugh the suppression of microglial activity than by inhibiting the form ation of SP or neurofibrillary tangles.