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Plasma levels of beta-amyloid(1-40), beta-amyloid(1-42), and total beta-amyloid remain unaffected in adult patients with hypercholesterolemia after treatment with statins.

Journal article
Authors Kina Höglund
Olov Wiklund
Hugo Vanderstichele
Oliver Eikenberg
Eugeen Vanmechelen
Kaj Blennow
Published in Archives of neurology
Volume 61
Issue 3
Pages 333-7
ISSN 0003-9942
Publication year 2004
Published at Wallenberg Laboratory
Institute of Clinical Neurosciences, Section of Experimental Neuroscience
Pages 333-7
Language en
Links dx.doi.org/10.1001/archneur.61.3.33...
Keywords Adult, Aged, Amyloid beta-Protein, blood, Anticholesteremic Agents, therapeutic use, Cross-Over Studies, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, methods, Female, Heptanoic Acids, therapeutic use, Humans, Hypercholesterolemia, blood, drug therapy, Lipids, blood, Male, Middle Aged, Peptide Fragments, blood, Prospective Studies, Pyrroles, therapeutic use, Simvastatin, therapeutic use, Time Factors
Subject categories Psychiatry

Abstract

BACKGROUND: Epidemiological studies suggest that statins reduce the risk of developing Alzheimer disease. Cell and animal experiments have revealed a connection between cholesterol metabolism and the processing of amyloid precursor protein. To our knowledge, the mechanism for statins in risk reduction of Alzheimer disease is unknown. OBJECTIVE: To test the effect of statin treatment on beta-amyloid (A beta) metabolism in humans. DESIGN: A prospective, randomized, dose-finding 36-week treatment trial with statins. Plasma samples were taken at baseline (week 0) and at weeks 6, 12, and 36. SETTING: Outpatient clinical study at a university hospital. PATIENTS: Thirty-nine patients who met the criteria for hypercholesterolemia. INTERVENTIONS: Patients were randomized to oral treatment with either simvastatin or atorvastatin calcium according to the following regimen: simvastatin, 40 mg/d, or atorvastatin, 20 mg/d, for 6 weeks; followed by simvastatin, 80 mg/d, or atorvastatin, 40 mg/d, for 6 weeks; and finally, simvastatin, 80 mg/d, or atorvastatin, 80 mg/d, for 24 weeks. MAIN OUTCOME MEASURES: Plasma levels of A beta(1-40) and A beta(1-42) were measured using 2 enzyme-linked immunosorbent assays, and total A beta was quantified by Western blotting. RESULTS: Treatment with both statins reduced total plasma cholesterol levels by 56% (P =.00). The plasma levels of A beta(1-40), A beta(1-42), and total A beta were stable in individual patients during the treatment period. No significant change in the level of A beta(1-40), A beta(1-42), or total A beta was found. CONCLUSION: This study questions the effect of statins on the processing of amyloid precursor protein in humans.

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