INDOMETHACIN REVERSES THE MICROGLIAL RESPONSE TO AMYLOID BETA-PROTEIN

Alzheimer's disease (AD) brains display intense microglial immunoreact ivity in the area of senile plaques, suggesting that amyloid P-protein may stimulate microglial infiltration. The activated microglia may mo dulate an immune response in the brain. Non-steroidal anti-inflammator y drugs (NSAIDs) are candidate therapeutics for AD because their effec ts on immune system components may influence the course of the disease . The present study examined the effects of an NSAID (indomethacin) on amyloid beta-protein-induced microglial infiltration. Amyloid beta-pr otein was chronically infused into rat lateral ventricles for 2 weeks. Extracellular amyloid beta-protein deposited along the lining and dif fused into the tissue surrounding the lateral ventricle. Immunocytoche mical staining showed that animals receiving amyloid beta-protein exhi bited dramatic microglial response when compared to vehicle-infused ra ts. Activated microglia surrounded immunopositive amyloid beta-protein deposits, hut this response was significantly attenuated in animals r eceiving either concurrent ICV or subcutaneous (s.c.) treatment with i ndomethacin. These results suggest that chronic amyloid beta-protein i nfusion induces the proliferation of activated microglia and that indo methacin may be an effective treatment for inhibiting microglial proli feration. (C) 1998 Elsevier Science Inc.