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

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.