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Effect of statins on beta-amyloid metabolism in humans: potential importance for the development of senile plaques in Alzheimer's disease.

Journal article
Authors Kina Höglund
Anders Wallin
Kaj Blennow
Published in Acta neurologica Scandinavica. Supplementum
Volume 185
Pages 87-92
ISSN 0065-1427
Publication year 2006
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 87-92
Language en
Links dx.doi.org/10.1111/j.1600-0404.2006...
Keywords Alzheimer Disease, etiology, prevention & control, Amyloid beta-Protein, metabolism, Brain, drug effects, metabolism, Cholesterol, metabolism, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, pharmacology, therapeutic use, Senile Plaques, drug effects
Subject categories Neurochemistry

Abstract

According to the amyloid cascade hypothesis, both familial and sporadic Alzheimer's disease (AD) is caused by the toxic effect of over-production and/or aggregation of beta-amyloid (Abeta). Recent cell and animal studies have linked the production of Abeta to high levels of cholesterol and the use of statins, compounds inhibiting the de novo synthesis of cholesterol. Epidemiological studies have also supported such linkage by showing a reduced prevalence of AD for subjects taking statins. A limited number of clinical studies have been published trying to elucidate the effect of statin treatment on amyloid precursor protein (APP) processing and metabolism of brain cholesterol in AD in humans and this review focuses on the current state of these clinical studies. The results are contradictory, but the overall interpretation suggests that statin treatment probably does not have a direct impact through lowering of cholesterol on the APP processing and Abeta production in humans. To confirm this, further clinical studies needs to be performed with extended treatment periods and where several parameters (lipid profile, lipoproteins, sterols, biomarkers related to AD and APP metabolites) are analyzed, both in the cerebrospinal fluid and plasma. The pleiotropic effects of statins should be investigated further. One approach is presented in this review.

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