MS4A6E and Alzheimer Disease

In recent multi‐patient studies, MS4A6E has emerged as a gene significantly associated with Alzheimer disease. Aggregate SNP analyses in large cohorts have demonstrated robust association signals, with evidence derived from both male‐specific analyses (PMID:27005436) and independent population studies involving 634 subjects (PMID:28199971). These findings provide strong statistical support despite the absence of classical family‐based segregation data.

The genetic evidence is bolstered by comprehensive case‑control analyses where multiple single nucleotide polymorphisms in the MS4A6E region showed significant disease association. In one study, aggregate variation across candidate AD genes was linked to cognitive decline using rigorous statistical methods, indicating that the association with MS4A6E is not spurious but part of a broader genetic risk profile for Alzheimer disease (PMID:27005436).

A further study performed in a Taiwanese population of 634 older adults examined the interaction between genetic variants and lifestyle factors. Although only a subset of variants reached significance after correction, the inclusion of MS4A6E among the AD‐associated genes suggests its contributory role in cognitive aging, emphasizing the gene’s relevance in diverse ethnic cohorts (PMID:28199971).

Complementing the statistical associations, functional experiments have provided moderate support for the pathogenicity of MS4A6E. Transcriptome‑wide association studies in lipopolysaccharide‑stimulated monocytes revealed altered gene expression patterns that replicate in independent datasets, thereby linking MS4A6E expression changes to Alzheimer disease pathology (PMID:33959712).

While classical segregation data is lacking (with 0 additional affected relatives reported), the convergence of genetic and functional evidence across multiple, independent studies forms a coherent narrative. The aggregate data strongly implicates MS4A6E in the molecular mechanisms underlying Alzheimer disease, likely through mechanisms affecting immune and cellular stress responses.

Key take‑home: MS4A6E represents a robust genetic risk factor for Alzheimer disease, and its integration into diagnostic panels may facilitate improved risk stratification and personalized therapeutic strategies.

References

• Age (Dordrecht, Netherlands) • 2016 • Gene-based aggregate SNP associations between candidate AD genes and cognitive decline PMID:27005436
• Oncotarget • 2017 • Association and interaction effects of Alzheimer's disease-associated genes and lifestyle on cognitive aging in older adults in a Taiwanese population PMID:28199971
• Brain Communications • 2021 • Defining functional variants associated with Alzheimer's disease in the induced immune response PMID:33959712

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