Alzheimer's disease neuropathology is characterised by b-amyloid plaques and neurofibrillary tangles. Inhibition of b-amyloid accumulation may be essential for effective therapy in Alzheimer's disease. In this study we have treated transgenic mice carrying the Swedish mutation of human amyloid precursor protein [Tg(Hu.APP695.K670N-M671L)2576], which develop brain b-amyloid deposits, with nicotine in drinking fluid (200 lg/mL) from 9-14.5 months of age (5.5 months). A significant reduction in amyloid b peptide 1-42 positive plaques by more than 80% (p < 0.03) was observed in the brains of nicotine treated compared to sucrose treated transgenic mice. In addition, there was a selective reduction in extractable amyloid b peptides in nicotine treated mice; cortical insoluble 1-40 and 1-42 peptide levels were lower by 48 and 60%, respectively (p < 0.005), whilst there was no significant change in soluble 1-40 or 1-42 levels. The expression of glial fibrillary acidic protein was not affected by nicotine treatment. These results indicate that nicotine may effectively reduce amyloid b peptide aggregation in brain and that nicotinic drug treatment may be a novel protective therapy in Alzheimer's disease.

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