La Alzheimer's disease and related dementias are complex pathologies, in which the genetic plays a major role. A significant international collaboration, coordinated in particular by researchers from the unit INSERM UMR1167 led by Dr. Jean-Charles Lambert at the Pasteur Institute campus in Lille, recently published in Nature Genetics one of the largest genetic studies conducted to date on these pathologies.
An unprecedentedly large-scale genetic study to better understand Alzheimer's disease
Drawing on data from several large international consortia focusing on cohorts of patients of European ancestry, the researchers conducted a meta-analysis in order to better distinguish the genetic factors specifically involved in Alzheimer's disease from those more broadly associated with related dementias. The study is based on the analysis of 128,000 patients with Alzheimer's disease, associated dementias, or those considered "proxy" (i.e., individuals with a close relative affected), as well as nearly 850,000 control patients.
This analysis made it possible to identify 91 regions of the genome associated with the risk of developing Alzheimer's disease or a related dementia. The researchers also confirmed the involvement of several already known genetic regions, while highlighting 16 new regions, never before associated with these pathologies in European populations. Among all these regions of the genome, 56 are specifically detected in diagnosed clinical forms of Alzheimer's disease.
New perspectives for diagnostics and personalized medicine
Beyond the identification of new genetic factors, the results show a strong association with several biological pathways already implicated in Alzheimer's disease, including:
- la tau protein,
- peptides amyloid,
- the lipids,
- theimmunity,
- the endosomal/lysosomal pathways.
The authors also developed polygenic risk scores incorporating all identified genetic regions, with the exception of the APOE gene, the main known genetic factor in the disease. These scores appear to reflect Alzheimer's disease more specifically than other neurodegenerative pathologies, thus reinforcing the specificity of these results for the disease.
These discoveries are all the more important given that Alzheimer's disease affects nearlyone million people in France and mainly affects the elderlyIn a context of population aging and increased life expectancy, better understanding the biological mechanisms of disease is a major challenge for improving patient stratification, refining diagnosis and developing personalized medicine approaches better suited to each individual.
U1167: “Integrative epidemiological and molecular approaches aimed at improving the understanding of chronic diseases related to aging”
INSERM – University of Lille – Lille University Hospital – Pasteur Institute of Lille
EADB., EADI., Bonn. et al. Consensus meta-analysis of genome-wide association studies for Alzheimer's disease and related dementias. Nat Genet (2026). Consensus meta-analysis of genome-wide association studies for Alzheimer's disease and related dementia…
