Protective genetic variants against Alzheimer's disease
(2025) The Lancet Neurology — Vol. 24, n° 6, p. 524-534 (2025)
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- Authors
- Abstract
- (en) Genetic studies can offer powerful insights for the development of disease-modifying therapies for Alzheimer's disease. Protective genetic variants that delay the onset of cognitive impairment have been found in people with sporadic Alzheimer's disease and in carriers of mutations that usually cause autosomal-dominant Alzheimer's disease in mid-life. The study of families who carry autosomal dominant mutations provides a unique opportunity to uncover genetic modifiers of disease progression, including rare variants in genes such as APOE and RELN. Understanding how these variants confer protection can help identify the biological pathways that contribute to cognitive resilience, such as the heparan-sulphate proteoglycan-APOE receptor pathway, the TREM-2-driven signalling pathways in the microglia, and phagocytosis. Therapies able to replicate the beneficial effects of these natural defences could provide novel strategies for slowing or preventing the progression of Alzheimer's disease.
- Affiliations
Massachusetts General Hospital Department of Psychiatry, Harvard Medical School
Citations
Claudia Marino, Malotaux, V., Averi Giudicessi, David Aguillon, Diego Sepulveda-Falla, Francisco Lopera, & Yakeel T Quiroz. (2025). Protective genetic variants against Alzheimer’s disease. The Lancet Neurology, 24(6), 524-534. https://doi.org/10.1016/s1474-4422(25)00116-4 (Original work published 2025)