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Simvastatin strongly reduces levels of Alzheimer's disease β-amyloid peptides Aβ42 and Aβ40 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 Aβ42 levels and the - ɛ4 allele of the lipid-carrier apolipoprotein E are regarded as risk - factors for sporadic and...

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Main Authors: Faßbender, Klaus (Author) , Simons, M. (Author) , Bergmann, Carina (Author) , Stroick, Mark Gregor (Author) , Lütjohann, D. (Author) , Keller, P. (Author) , Runz, Heiko (Author) , Kühl, Sandra (Author) , Bertsch, Thomas (Author) , Bergmann, K. von (Author) , Hennerici, Michael G. (Author) , Beyreuther, Konrad (Author) , Hartmann, Tobias (Author)
Format: Article (Journal)
Language:English
Published: [May 8, 2001]
In: Proceedings of the National Academy of Sciences of the United States of America
Year: 2001, Volume: 98, Issue: 10, Pages: 5856-5861
ISSN:1091-6490
DOI:10.1073/pnas.081620098
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1073/pnas.081620098
Verlag, lizenzpflichtig, Volltext: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC33303/
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Author Notes:K. Fassbender, M. Simons, C. Bergmann, M. Stroick, D. Lütjohann, P. Keller, H. Runz, S. Kühl, T. Bertsch, K. von Bergmann, M. Hennerici, K. Beyreuther, and T. Hartmann

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520 |a Recent epidemiological studies show a strong reduction in the - incidence of Alzheimer's disease in patients treated with - cholesterol-lowering statins. Moreover, elevated Aβ42 levels and the - ɛ4 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 Aβ42 - and Aβ40 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 - Aβ42 and Aβ40 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 - Aβ42 may provide the mechanism for the observed reduced incidence of - dementia in statin-treated patients and may open up avenues for - therapeutic interventions. 
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