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

Article type: Research Article

Authors: Wei, Shan^{a; 1} | Dang, Liangjun^{a; 1} | Gao, Fan^b | Wang, Jingyi^c | Wang, Jin^{a; *} | Qu, Qiumin^{a; d; *}

Affiliations: [a] Department of Neurology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China | [b] Clinical research center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China | [c] Huyi Hospital of Traditional Chinese Medicine, Xi’an, China | [d] Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

Correspondence: [*] Correspondence to: Jin Wang and Qiumin Qu, Department of Neurology, The First Affiliated Hospital of Xi’an Jiaotong University, 277 West Yanta Rd, Xi’an 710061, China. Tel./Fax: +86 029 8532 4083; E-mail: [email protected]. (J Wang), E-mail: [email protected]. (Q. Qu)

Note: [1] These authors contributed equally to this work.

Abstract: 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, ΔAβ42 levels (the change of Aβ42 levels from baseline at week 12) increased more and ΔsRAGE 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 ΔAβ42 and ΔsRAGE 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.

Keywords: Alzheimer’s disease, hyperlipidemia, plasma amyloid-β, simvastatin, soluble low-density lipoprotein receptor-related protein-1, soluble receptor of advanced glycation end products

DOI: 10.3233/JAD-220240

Journal: Journal of Alzheimer's Disease, vol. 90, no. 1, pp. 349-362, 2022