Research article summary (published 29 Nov 2006):

Simvastatin enhances learning and memory independent of amyloid load in mice.

Full Abstract

OBJECTIVE: Normal aging is often associated with a decline in learning and memory functions. This decline is manifested to a much greater extent in Alzheimer's disease. Recent studies have indicated statins, a class of cholesterol-lowering drugs, as a potential therapy for Alzheimer's disease. Our objective was to determine whether administering a statin drug (simvastatin) would protect against the development of behavioral deficits in an established mouse model of Alzheimer's disease. METHODS: Tg2576 mice and their nontransgenic littermates were treated with simvastatin and assessed by behavioral tests and biochemical analyses. RESULTS: Simvastatin treatment not only reversed learning and memory deficits in the Tg2576 mice, but also enhanced learning and memory in the nontransgenic mice. Moreover, levels of amyloid beta protein in the brains of treated mice did not differ from those of untreated mice. Simvastatin treatment was associated with increased expression levels of protein kinase B (Akt) and endothelial nitric oxide synthase in the mouse brain. INTERPRETATION: Our findings demonstrate that the effects of simvastatin on learning and memory are independent of amyloid beta protein levels. The mechanisms by which simvastatin exerts its beneficial effects may be related to modulation of signaling pathways in memory formation.

Author information

Author/s: Li, Ling (L); Cao, Dongfeng (D); Kim, Helen (H); Lester, Robin (R); Fukuchi, Ken-Ichiro (K);

Affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. lili(-atsign-)uab.edu

Grants: AG016582 (Agency:NIA NIH HHS) ; AG025949 (Agency:NIA NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Annals of neurology (Ann Neurol), published in United States. (Language: eng)

Reference: 2006-Dec; vol 60 (issue 6) : pp 729-39

Dates: Created 2007/01/03; Completed 2007/02/26; Revised 2007/12/03;

PMID: 17192930, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Alzheimer Disease - drug therapy; physiopathology; psychology Animals Anticholesteremic Agents - pharmacology; therapeutic use Brain - drug effects; pathology; physiopathology Cholesterol - metabolism Cytoprotection - drug effects; physiology Disease Models, Animal Female Learning - drug effects; physiology Learning Disorders - drug therapy; pathology; physiopathology Memory - drug effects; physiology

Memory Disorders - drug therapy; pathology; physiopathology Mice Mice, Inbred C57BL Mice, Transgenic Neuroprotective Agents - pharmacology; therapeutic use Nitric Oxide Synthase Type III - drug effects; metabolism Proto-Oncogene Proteins c-akt - drug effects; metabolism Senile Plaques - drug effects; metabolism; pathology Signal Transduction - drug effects; physiology Simvastatin - pharmacology; therapeutic use Treatment Outcome

Associated Chemicals: Anticholesteremic Agents (0) ; Neuroprotective Agents (0) ; Cholesterol (57-88-5) ; Simvastatin (79902-63-9) ; Nitric Oxide Synthase Type III (EC 1.14.13.39) ; Proto-Oncogene Proteins c-akt (EC 2.7.1.37)

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