普罗布考对高脂血症患者血浆β淀粉样蛋白转运的影响：一项为期12周的随机、双盲、安慰剂对照试验。

Effects of Probucol on plasma amyloid-β transport in patients with hyperlipidemia: a 12-week randomized, double-blind, placebo-controlled trial.

作者信息

Dang Liangjun, Wei Shan, Zhao Yi, Zhou Rong, Shang Suhang, Gao Fan, Wang Jingyi, Wang Jin, Qu Qiumin

机构信息

Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

出版信息

Lipids Health Dis. 2024 Dec 19;23(1):410. doi: 10.1186/s12944-024-02398-1.

DOI:10.1186/s12944-024-02398-1

PMID:39702132

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11657980/

Abstract

BACKGROUND

Although dyslipidemia has been acknowledged as a risk factor for Alzheimer's disease (AD), the effects of lipid-lowering drugs on AD have not been determined. The primary pathophysiological hallmark of AD is the deposition of amyloid-β (Aβ) plaques in the brain. Plasma Aβ levels are influenced by the transport of Aβ from the central nervous system to the peripheral blood. This study investigates the effects of Probucol, a lipid-lowering and antioxidant drug, on plasma Aβ transport.

METHODS

A total of 120 hyperlipidemic patients with normal cognition were randomly assigned (1:1 ratio) to receive either Probucol (1000 mg daily for 12 weeks) or a placebo. Plasma Aβ, soluble receptor of advanced glycation end products (sRAGE), and fasting lipid profiles were measured at baseline and every 6 weeks.

RESULTS

A total of 108 participants completed the study, with 55 in the Probucol group. The cohort consisted of 58 (53.7%) women, with a mean age of 58.4 ± 8.0 (range, 45-80) years. After 12 weeks of treatment, the changes in plasma Aβ and sRAGE levels significantly differed between the Probucol and placebo groups (ΔAβ: β = 6.827, P = 0.030; ΔsRAGE: β = 98.668, P = 0.004). Furthermore, ΔsRAGE was positively correlated with the change in Aβ (β = 0.018, P = 0.048). When adjusted for ΔsRAGE, the effect of Probucol on plasma Aβ levels was attenuated (β = 5.065, P = 0.116). In the Probucol group only, ΔsRAGE was significantly correlated with oxidized low-density lipoproteins (β = 4.27, P = 0.011), total cholesterol (β = 67.50, P = 0.046), and low-density lipoproteins (β = - 91.01, P = 0.011).

CONCLUSIONS

Daily oral administration of Probucol (1000 mg) for 12 weeks significantly increased plasma Aβ levels, likely through modulation of sRAGE. This effect may be attributed to the antioxidant and lipid-lowering properties of Probucol. These findings suggest that Probucol could potentially serve as a protective agent against the pathological processes of AD.

TRIAL REGISTRATION

This study was registered on the Chinese Clinical Trial Registry platform in June 2019 (Trial registration number: ChiCTR-1900023542).

摘要

背景

尽管血脂异常已被公认为是阿尔茨海默病（AD）的一个危险因素，但降脂药物对AD的影响尚未确定。AD的主要病理生理特征是大脑中β淀粉样蛋白（Aβ）斑块的沉积。血浆Aβ水平受Aβ从中枢神经系统向外周血转运的影响。本研究调查了降脂抗氧化药物普罗布考对血浆Aβ转运的影响。

方法

总共120名认知正常的高脂血症患者被随机分配（1:1比例）接受普罗布考（每日1000毫克，共12周）或安慰剂治疗。在基线和每6周时测量血浆Aβ、晚期糖基化终产物可溶性受体（sRAGE）和空腹血脂谱。

结果

共有108名参与者完成了研究，普罗布考组有55人。该队列包括58名（53.7%）女性，平均年龄为58.4±8.0（范围45 - 80）岁。治疗12周后，普罗布考组和安慰剂组血浆Aβ和sRAGE水平的变化有显著差异（ΔAβ：β = 6.827，P = 0.030；ΔsRAGE：β = 98.668，P = 0.004）。此外，ΔsRAGE与Aβ的变化呈正相关（β = 0.018，P = 0.048）。在对ΔsRAGE进行校正后，普罗布考对血浆Aβ水平的影响减弱（β = 5.065，P = 0.116）。仅在普罗布考组中，ΔsRAGE与氧化型低密度脂蛋白（β = 4.27，P = 0.011）、总胆固醇（β = 67.50，P = 0.046）和低密度脂蛋白（β = - 91.01，P = 0.011）显著相关。