Effects of Simvastatin on Plasma Amyloid-β Transport in Patients with Hyperlipidemia: A 12-Week Randomized, Double-Blind, Placebo-Controlled Trial

Background: Abnormal blood lipids are associated with cognitive impairment and amyloid-β (Aβ) deposition in the brain. However, the effects of statins on Alzheimer’s disease (AD) have not been determined. Objective: Considering that plasma Aβ are related to Aβ deposition in the brain, we investigated the effects of simvastatin on plasma Aβ transport. Methods: This was a randomized, double-blind, placebo-controlled trial. One hundred and twenty patients with hyperlipidemia were randomly assigned to receive 40 mg of simvastatin per day or matching placebo for 12 weeks (sixty patients per group). Plasma Aβ, sLRP1, sRAGE, and lipid levels were measured at baseline and at the 6-week and 12-week visits. Results: The ITT database ultimately included 108 participants (placebo group: n = 53; simvastatin group: n = 55) and 64 (59.3%) were women, ranging in age from 45 to 75 years (mean 57.2 ± 6.9 years). Multiple linear regression analysis showed that, after 12 weeks of follow-up, compared with the placebo group, ▲Aβ₄₂ levels (the change of Aβ₄₂ levels from baseline at week 12) increased more and ▲sRAGE levels decreased more in the simvastatin group (Aβ₄₂: β = 5.823, p = 0.040; sRAGE: β = –72.012, p = 0.031), and a significant negative association was found between ▲Aβ₄₂ and ▲sRAGE levels (β = –0.115, p = 0.045). In addition, generalized estimation equation analysis showed that triglycerides levels were negatively correlated with Aβ₄₀ (β = –16.79, p = 0.023), Aβ₄₂ (β = –6.10, p = 0.001), and sRAGE (β = –51.16, p = 0.003). Conclusion: Daily oral simvastatin (40 mg/day) in patients with hyperlipidemia for 12 weeks can significantly increase plasma Aβ₄₂ levels compared with placebo, which was associated with reduced triglycerides and sRAGE levels, indicating that statins may affect plasma Aβ transport.