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November 8, 2025Alzheimer s & Dementia5 citationsOpen Access

Shared genes and pathways in dementia: Insights from genome‐wide association studies

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KLKyle J. LoiNRNoah RadtkeCKChloe Kiriluk

Key Points

  • Dementia shows shared genetic pathways and loci, revealing insights into neurodegeneration.
  • Analysis of genome-wide association studies emphasizes lipid metabolism and immune responses in dementia.
  • Examining genetic heterogeneity and utilizing polygenic risk scores could improve disease prediction.
  • Integrating diverse populations may enhance future research and therapeutic strategies in dementia.

Abstract

Abstract Dementia, a collective term for neurodegenerative disorders marked by cognitive decline, affects millions worldwide, and is expected to rise significantly in prevalence. Genome‐wide association studies (GWASs), as highlighted in this review, have revolutionized our understanding of dementia by identifying contributing genetic loci and pathways, including for Alzheimer's disease, vascular dementia, frontotemporal lobar dementia, and Lewy body dementia. This review critically analyzes published findings to shed insight on shared genes and pathways, encompassing lipid metabolism, immune responses, lysosomal mechanisms, and ionic homeostasis, which underlie neurodegeneration in dementia. We discuss methodological advances, challenges posed by genetic heterogeneity and population diversity, and the utility of polygenic risk scores in disease prediction. Furthermore, the importance of integrating tissue‐specific expression data and non‐European ancestral study cohorts is emphasized. Finally, this review outlines the next steps for advancing dementia research through GWASs and genetic insights. Highlights Genome‐wide association studies (GWASs) provide insight into the complex genetic architecture underlying dementia. Synthesizing GWASs across dementia subtypes highlights shared mechanisms. Identifying shared pathways may guide therapeutic development. Limitations exist and future GWASs may benefit from use of diverse populations.

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Cite This Study

Loi et al. (2025) studied this question.

synapsesocial.com/papers/690e8b75a5b062d7a4e73845https://doi.org/10.1002/alz.70845
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