Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer's disease

The brain in Alzheimer's disease (AD) shows a chronic inflammatory response characterized by activated glial cells and increased expression of cytokin es and complement factors surrounding amyloid deposits. Several epidemiolog ical studies have demonstrated a reduced risk for AD in patients using nons teroidal anti-inflammatory drugs (NSAIDs), prompting further inquiries abou t how NSAIDs might influence the development of AD pathology and inflammati on in the CNS. We tested the impact of chronic orally administered ibuprofe n, the most commonly used NSAID, in a transgenic model of AD displaying wid espread microglial activation, age-related amyloid deposits, and dystrophic neurites. These mice were created by overexpressing a variant of the amylo id precursor protein found in familial AD. Transgene-positive (Tg+) and neg ative (Tg-) mice began receiving chow containing 375 ppm ibuprofen at 10 mo nths of age, when amyloid plaques first appear, and were fed continuously f or 6 months. This treatment produced significant reductions in final interl eukin-1 beta and glial fibrillary acidic protein levels, as well as a signi ficant diminution in the ultimate number and total area of beta-amyloid dep osits. Reductions in amyloid deposition were supported by ELISA measurement s showing significantly decreased SDS-insoluble A beta. Ibuprofen also decr eased the numbers of ubiquitin-labeled dystrophic neurites and the percenta ge area per plaque of antiphosphotyrosine-labeled microglia. Thus, the anti -inflammatory drug ibuprofen, which has been associated with reduced AD ris k in human epidemiological studies, can significantly delay some forms of A D pathology, including amyloid deposition, when administered early in the d isease course of a transgenic mouse model of AD.