Simvastatin strongly reduces levels of Alzheimer's disease beta-amyloid peptides A beta 42 and A beta 40 in vitro and in vivo

Recent epidemiological studies show a strong reduction in the incidence of Alzheimer's disease in patients treated with cholesterol-lowering statins. Moreover, elevated A beta 42 levels and the epsilon4 allele of the lipid-ca rrier apolipoprotein E are regarded as risk factors for sporadic and famili al Alzheimer's disease. Here we demonstrate that the widely used cholestero l-lowering drugs simvastatin and lovastatin reduce intracellular and extrac ellular levels of A beta 42 and A beta 40 peptides in primary cultures of h ippocampal neurons and mixed cortical neurons. Likewise, guinea pigs treate d with high doses of simvastatin showed a strong and reversible reduction o f cerebral A beta 42 and A beta 40 levels in the cerebrospinal fluid and br ain homogenate, These results suggest that lipids are praying an important role in the development of Alzheimer's disease. Lowered levels of A beta 42 may provide the mechanism for the observed reduced incidence of dementia i n statin-treated patients and may open up avenues for therapeutic intervent ions.