Plasma Levels of β-Amyloid(1-40), β-Amyloid(1-42), and Total β-Amyloid Remain Unaffected in Adult Patients With Hypercholesterolemia After Treatment With Statins

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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 β-amyloid (Aβ) 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 Aβ(1-40) and Aβ(1-42) were measured using 2 enzyme-linked immunosorbent assays, and total Aβ was quantified by Western blotting. Results Treatment with both statins reduced total plasma cholesterol levels by 56% (P = .00). The plasma levels of Aβ(1-40), Aβ(1-42), and total Aβ were stable in individual patients during the treatment period. No significant change in the level of Aβ(1-40), Aβ(1-42), or total Aβ was found. Conclusion This study questions the effect of statins on the processing of amyloid precursor protein in humans.