A cholesterol-lowering drug reduces β-amyloid pathology in a transgenic mouse model of Alzheimer's disease

Clinical, epidemiological, and laboratory studies suggest that cholesterol may play a role in the pathogenesis of Alzheimer's disease (AD). Transgenic mice exhibiting an Alzheimer's beta -amyloid phenotype were treated with the cholesterol-lowering drug BM15.766 and tested for modulation of beta -amyloid levels. BM15.766 treatment reduced plasma cholesterol, brain A beta peptides, and beta -amyloid load by greater than twofold. A strong, positive correlation between the amount of plasma cholesterol and A beta was observed. Furthermore, drug treatment reduced the amyloidogenic processing of the amyloid precursor protein, suggesting alterations in processing in response to cholesterol modulation. This study demonstrates that hypocholesterolemia is associated with reduced A beta accumulation suggesting that lowering cholesterol by pharmacological means may be an effective approach for reducing the risk of developing AD. (C) 2001 Academic Press.