Impact of APOE ε4 Genotype Load on Cognitive Function and Lipid Metabolism in Patients With Cerebral Small Vessel Disease.

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Annals of Clinical and Translational Neurology Pub Date : 2025-10-15 DOI:10.1002/acn3.70224

Tingru Jin, Haocheng Yang, Feng Liu, Sihao Lin, Junru Hu, Jian Wang, Yulan Gou

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引用次数: 0

Abstract

Background: Apolipoprotein ε4 (APOE ε4) is a potent genetic risk factor for Alzheimer's disease (AD). However, its role in cerebral small vessel disease (CSVD) remains unclear. Given the clinical and pathological similarities between CSVD and AD, this study aimed to investigate the associations of APOE ε4 gene dosage with cognitive function and dyslipidemia in CSVD patients, and to explore whether lipid disturbances mediate the effect of APOE ε4 on white matter hyperintensity (WMH) burden and cognitive impairment.

Methods: The study was a retrospective study. A total of 717 inpatients with CSVD admitted to the Department of Neurology, Wuhan No.1 Hospital, from January 2023 to January 2025 were enrolled. Associations among APOE ε4 gene dosage, cognitive function, lipid metabolism, and WMH were analyzed.

Results: The number of APOE ε4 alleles showed a significant negative correlation with MMSE and MoCA scores (p < 0.001), and a dose-dependent positive correlation with the risk of cognitive impairment and WMH severity, independent of traditional vascular risk factors. Lipid analysis indicated that APOE ε4 was an independent risk factor for elevated low-density lipoprotein cholesterol (LDL-C), but had no significant associations with high-density lipoprotein cholesterol (HDL-C) or triglycerides (TG). Mediation analysis suggested that LDL-C may mediate the indirect detrimental effect of APOE ε4 on cognitive function.

Conclusion: APOE ε4 gene dosage is an independent risk factor for cognitive decline and WMH in CSVD patients, independent of traditional vascular risk factors. APOE ε4 may indirectly impair cognitive function by elevating LDL-C levels to exacerbate atherosclerosis and cerebrovascular injury.

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APOE ε4基因型负荷对脑血管病患者认知功能及脂质代谢的影响

背景：载脂蛋白ε4 （APOE ε4）是阿尔茨海默病（AD）的重要遗传危险因素。然而，其在脑血管病（CSVD）中的作用尚不清楚。鉴于CSVD与AD在临床和病理上的相似性，本研究旨在探讨APOE ε4基因剂量与CSVD患者认知功能和血脂异常的关系，并探讨脂质紊乱是否介导APOE ε4对白质高强度（WMH）负担和认知功能障碍的影响。方法：采用回顾性研究。入选武汉市第一医院神经内科2023年1月至2025年1月住院的CSVD患者717例。分析APOE ε4基因剂量与认知功能、脂质代谢及WMH的相关性。结果：APOE ε4等位基因数量与MMSE和MoCA评分呈显著负相关(p)。结论：APOE ε4基因剂量是CSVD患者认知能力下降和WMH的独立危险因素，独立于传统血管危险因素。APOE ε4可能通过升高LDL-C间接损害认知功能，加重动脉粥样硬化和脑血管损伤。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Clinical and Translational Neurology Medicine-Neurology (clinical)

CiteScore

9.10

自引率

1.90%

发文量

218

审稿时长

8 weeks

期刊介绍： Annals of Clinical and Translational Neurology is a peer-reviewed journal for rapid dissemination of high-quality research related to all areas of neurology. The journal publishes original research and scholarly reviews focused on the mechanisms and treatments of diseases of the nervous system; high-impact topics in neurologic education; and other topics of interest to the clinical neuroscience community.