A cholesterol-lowering drug reduces beta-amyloid pathology in a transgenicmouse 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 t he cholesterol-lowering drug BM15.766 and tested for modulation of beta -am yloid levels. BM15.766 treatment reduced plasma cholesterol, brain A beta p eptides, and beta -amyloid load by greater than twofold. A strong, positive correlation between the amount of plasma cholesterol and A beta was observ ed. Furthermore, drug treatment reduced the amyloidogenic processing of the amyloid precursor protein, suggesting alterations in processing in respons e to cholesterol modulation. This study demonstrates that hypocholesterolem ia is associated with reduced A beta accumulation suggesting that lowering cholesterol by pharmacological means may be an effective approach for reduc ing the risk of developing AD. (C) 2001 Academic Press.