| Effects of simvastatin on cholesterol metabolism and Alzheimer disease biomarkers. | |
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MedLine Citation:
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PMID: 20473136 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Preclinical and epidemiologic studies suggest a protective effect of statins on Alzheimer disease (AD). Experimental evidence indicates that some statins can cross the blood-brain barrier, alter brain cholesterol metabolism, and may ultimately decrease the production of amyloid-beta (Abeta) peptide. Despite these promising leads, clinical trials have yielded inconsistent results regarding the benefits of statin treatment in AD. Seeking to detect a biological signal of statins effect on AD, we conducted a 12-week open-label trial with simvastatin 40 mg/d and then 80 mg/d in 12 patients with AD or amnestic mild cognitive impairment and hypercholesterolemia. We quantified cholesterol precursors and metabolites and AD biomarkers of Abeta and tau in both plasma and cerebrospinal fluid at baseline and after the 12-week treatment period. We found a modest but significant inhibition of brain cholesterol biosynthesis after simvastatin treatment, as indexed by a decrease of cerebrospinal fluid lathosterol and plasma 24S-hydroxycholesterol. Despite this effect, there were no changes in AD biomarkers. Our findings indicate that simvastatin treatment can affect brain cholesterol metabolism within 12 weeks, but did not alter molecular indices of AD pathology during this short-term treatment. |
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Authors:
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Alberto Serrano-Pozo; Gloria L Vega; Dieter Lütjohann; Joseph J Locascio; Marsha K Tennis; Amy Deng; Alireza Atri; Bradley T Hyman; Michael C Irizarry; John H Growdon |
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Publication Detail:
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Type: Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Alzheimer disease and associated disorders Volume: 24 ISSN: 1546-4156 ISO Abbreviation: Alzheimer Dis Assoc Disord Publication Date: 2010 Jul-Sep |
Date Detail:
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Created Date: 2010-08-27 Completed Date: 2011-01-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8704771 Medline TA: Alzheimer Dis Assoc Disord Country: United States |
Other Details:
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Languages: eng Pagination: 220-6 Citation Subset: IM |
Affiliation:
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Memory Disorders Unit, Department of Neurology and Massachusetts Alzheimer's Disease Research Center, Massachusetts General Hospital, Harvard Medical School, Boston , MA 02114, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged Alzheimer Disease / drug therapy*, metabolism Amyloid beta-Peptides / blood, cerebrospinal fluid Anticholesteremic Agents / administration & dosage, adverse effects Biological Markers / blood*, cerebrospinal fluid* Brain / metabolism Cholesterol / metabolism* Cognition Disorders / drug therapy, metabolism Female Humans Hydroxycholesterols / blood Hypercholesterolemia / drug therapy Male Middle Aged Simvastatin / administration & dosage*, adverse effects |
| Chemical | |
Reg. No./Substance:
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0/Amyloid beta-Peptides; 0/Anticholesteremic Agents; 0/Biological Markers; 0/Hydroxycholesterols; 474-73-7/24-hydroxycholesterol; 57-88-5/Cholesterol; 79902-63-9/Simvastatin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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