Simvastatin strongly reduces levels of Alzheimer's disease β-amyloid peptides Aβ42 and Aβ40 in vitro and in vivo
Top Cited Papers
- 10 April 2001
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 98 (10), 5856-5861
- https://doi.org/10.1073/pnas.081620098
Abstract
Recent epidemiological studies show a strong reduction in the incidence of Alzheimer's disease in patients treated with cholesterol-lowering statins. Moreover, elevated Abeta42 levels and the varepsilon4 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 Abeta42 and Abeta40 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 Abeta42 and Abeta40 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 Abeta42 may provide the mechanism for the observed reduced incidence of dementia in statin-treated patients and may open up avenues for therapeutic interventions.Keywords
This publication has 55 references indexed in Scilit:
- Cholesterol-dependent generation of a unique amyloid β-protein from apically missorted amyloid precursor protein in MDCK cellsBiochimica et Biophysica Acta (BBA) - Biomembranes, 1998
- βAPP γ-secretase and SREBP site 2 protease are two different enzymesNeuroReport, 1998
- Lack of apolipoprotein E dramatically reduces amyloid β-peptide depositionNature Genetics, 1997
- Cerebral changes and cerebrospinal fluid β-amyloid in Alzheimer's disease: a study with quantitative magnetic resonance imagingMolecular Psychiatry, 1997
- Analysis of Heterogeneous βA4 Peptides in Human Cerebrospinal Fluid and Blood by a Newly Developed Sensitive Western Blot AssayJournal of Biological Chemistry, 1996
- Alzheimer's Disease βA4 Protein Release and Amyloid Precursor Protein Sorting Are Regulated by Alternative SplicingPublished by Elsevier BV ,1996
- Amyloids and Are Generated Intracellularly in Cultured Human Neurons and Their Secretion Increases with MaturationJournal of Biological Chemistry, 1996
- Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset FamiliesScience, 1993
- Amyloid β-peptide is produced by cultured cells during normal metabolismNature, 1992
- Biochemical Changes and Morphological Alterations of the Liver in Guinea‐Pigs after Administration of Simvastatin (HMG CoA Reductase‐Inhibitor)Basic & Clinical Pharmacology & Toxicology, 1990