Multiple sclerosis as a genetic risk factor for Alzheimer's disease: Insights from Mendelian randomisation.

IF 3.4 Q3 CLINICAL NEUROLOGY

Neurodegenerative disease management Pub Date : 2025-10-01 Epub Date: 2025-07-20 DOI:10.1080/17582024.2025.2530350

Jai Kumar Rajavoor Muniswamy, Amrutha Reshi, Dibyendu Roy Chowdhury, Praveen Kumar-M

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Abstract

Background: Inflammation is implicated in neurodegeneration, but the causal link between multiple sclerosis and Alzheimer's disease remains unclear.

Objective: To investigate the genetic relationship between MS and AD using Mendelian Randomization and assess downstream molecular effects.

Methods: Two-sample MR was conducted using GWAS summary statistics, with IVW and MR Egger methods. Sensitivity analyses assessed pleiotropy and heterogeneity. eQTL and KEGG pathway analyses explored gene expression and functional relevance.

Results: Sixty-four SNPs from European MS GWAS were selected for MR analysis; an African American dataset showed no significant SNPs. IVW and MR-Egger indicated a positive causal association between MS and AD (p < 0.05). Pleiotropy (Egger β = -0.017, p = 0.002) was addressed using robust methods. eQTL analysis identified 41 genes, with KEGG enrichment implicating Th1/Th2 and Th17 differentiation pathways.

Conclusion: MS may increase AD risk via shared T-cell - mediated immunogenetic mechanisms.

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多发性硬化症是阿尔茨海默病的遗传风险因素：孟德尔随机化的见解。

背景：炎症与神经退行性变有关，但多发性硬化症与阿尔茨海默病之间的因果关系尚不清楚。目的：利用孟德尔随机化方法研究多发性硬化症与AD的遗传关系，并评估下游分子效应。方法：采用GWAS汇总统计，采用IVW法和MR Egger法对两样本进行MR分析。敏感性分析评估了多效性和异质性。eQTL和KEGG通路分析探讨了基因表达和功能相关性。结果：从欧洲MS GWAS中选择64个snp进行MR分析；非裔美国人数据集显示没有显著的snp。IVW和MR-Egger表明，MS和AD之间存在正因果关系（p p = 0.002）。eQTL分析鉴定出41个基因，其中KEGG富集涉及Th1/Th2和Th17分化途径。结论：MS可能通过共同的t细胞介导的免疫发生机制增加AD的风险。

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

Neurodegenerative disease management CLINICAL NEUROLOGY-

CiteScore

4.30

自引率

0.00%

发文量