Indomethacin Reverses the Microglial Response to Amyloid β-Protein

Alzheimer’s disease (AD) brains display intense microglial immunoreactivity in the area of senile plaques, suggesting that amyloid β-protein may stimulate microglial infiltration. The activated microglia may modulate an immune response in the brain. Non-steroidal anti-inflammatory drugs (NSAIDs) are candidate therapeutics for AD because their effects on immune system components may influence the course of the disease. The present study examined the effects of an NSAID (indomethacin) on amyloid β-protein-induced microglial infiltration. Amyloid β-protein was chronically infused into rat lateral ventricles for 2 weeks. Extracellular amyloid β-protein deposited along the lining and diffused into the tissue surrounding the lateral ventricle. Immunocytochemical staining showed that animals receiving amyloid β-protein exhibited dramatic microglial response when compared to vehicle-infused rats. Activated microglia surrounded immunopositive amyloid β-protein deposits, but this response was significantly attenuated in animals receiving either concurrent ICV or subcutaneous (s.c.) treatment with indomethacin. These results suggest that chronic amyloid β-protein infusion induces the proliferation of activated microglia and that indomethacin may be an effective treatment for inhibiting microglial proliferation.