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

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