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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 [Epsilon]4 allele of the lipid-carrier apolipoprotein E are regarded as risk factors for sporadic and familial Alzheimer's disease. Here we demonstrate that the widely used cholesterol-lowering drugs simvastatin and lovastatin reduce intracellular and extracellular levels of A[Beta]42 and A[Beta]40 peptides in primary cultures of hippocampal neurons and mixed cortical neurons. Likewise, guinea pigs treated with high doses of simvastatin showed a strong and reversible reduction of cerebral A[Beta]42 and A[Beta]40 levels in the cerebrospinal fluid and brain homogenate. These results suggest that lipids are playing 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 in statin-treated patients and may open up avenues for therapeutic interventions.

Gerstmann-Straussler-Scheinker (GSS) disease is an inherited degenerative disease of the nervous system. The disease, which appears to be inherited as an autosomal dominant trait, first appears between the fourth and seventh decades of life; dementia progresses gradually and after several years rigidity and bradykinesia (slow movement) set in. Psychosis, depression, and rapid weight loss are common at this stage; death usually follows the onset of rigidity by six months to two years. Occasional sporadic cases are observed, however. Neuropathologic findings include the presence of amyloid plaques in the cerebellum and the cerebral cortex. Amyloid plaques are a common pathological feature of Alzheimer's disease; the plaques observed in GSS disease are somewhat intermediate between those observed in Alzheimer's disease and those seen in the rare South Pacific infectious disease kuru. Immunocytochemical techniques have now been used to confirm the distinction between the plaques observed in GSS and those seen in Alzheimer's disease. Alzheimer's disease amyloid plaques are composed predominantly of a protein subunit called A4, which is also known as beta-protein. Antibodies to A4 protein failed to recognize any component of the plaques in GSS disease. Plaques from diseases such as kuru, Creutzfeldt-Jakob disease, and the animal disease scrapie contain a protein called prion protein, or PrP. Although some investigators feel that PrP is also a component of the so-called prions, or infectious proteins, which are conjectured to cause these diseases, this has not been conclusively verified. Antibodies to PrP, however, were found to recognize components of the amyloid plaques in patients with GSS. While tangled neurofibrils are a common neuropathologic feature of Alzheimer's disease, they are not frequently observed in many cases of GSS. However, among the affected family members in the present study, neurofibrillary tangles were found to be numerous. The results indicate that the neuropathological changes in this disease may vary among different family pedigrees and that the normal spectrum of Gerstmann-Straussler-Scheinker disease includes neurofibrillary tangles as well as amyloid plaques. (Consumer Summary produced by Reliance Medical Information, Inc.)