03 Aug 2000

Epidemiological studies have hinted strongly that nonsteroidal anti-inflammatory drugs (NSAIDs) might delay the progression of Alzheimer's disease. In the August 1 issue of the Journal of Neuroscience, evidence for this therapeutic option is extended to an experimental model of AD, as Greg Cole and colleagues at UCLA and at the University of Minnesota find that ibuprofen can reduce plaque burden and inflammation in transgenic AD mice.

Transgenic mice developed in coauthor Karen Hsiao Ashe's laboratory express amyloid precursor protein from a kindred with familial AD. The mice have amyloid pathology, as well as activated microglia, a characteristic of chronic inflammation. However, when they were fed ibuprofen beginning at 10 months of age (the age at which plaques appear), the mice exhibited significant reductions (relative to nontreated mice) in the number and total area of amyloid-β depositions, as well as reductions in markers of inflammation (e.g., interleukin-1β [IL-1β], glial fibrillary acidic protein [GFAP], activated neurites). They also had fewer degenerating nerve processes (as determined by ubiquitin labeling).

In addition to providing the first evidence of NSAID utility in a transgenic AD model, the data can be brought to bear on the question of whether ibuprofen and its relatives counteract inflammation that leads to plaque formation, or whether they combat inflammation instigated by plaques already formed. This study offers strong support to the theory that NSAIDs prevent plaque formation, although it does not rule out an effect on inflammation initiated by the plaques themselves, say the authors.—Hakon Heimer