An international collaboration of genetic researchers has identified more than 90 genetic regions associated with the risk of Alzheimer’s disease and related dementias. The large-scale meta-analysis reveals new biological insights into the disease, highlighting the important roles of immune processes, beta-amyloid and tau biology, and lipid metabolism.
Alzheimer’s disease is the most common cause of dementia worldwide, and its development is influenced by a complex interplay of genetic and environmental factors. Understanding the genetic architecture of the disease is essential for improving diagnosis, risk prediction, and the development of targeted therapies. In this study, researchers combined genome-wide association data from nearly million individuals of European ancestry, including over 128,000 Alzheimer’s disease cases and nearly 850,000 controls. The study was conducted as a collaborative effort involving major international consortia, including the European Alzheimer and Dementia Biobank (EADB), the Alzheimer’s Disease Genetics Consortium (ADGC), and the FinnGen project, among others. By integrating data across 52 studies and several large biobanks, the researchers aimed to refine the genetic landscape of Alzheimer’s disease and identify new risk variants.
Newly identified genetic regions deepen understanding of disease mechanisms
Published in Nature Genetics, the study identified 91 genetic loci associated with Alzheimer’s disease and related dementias, including 16 previously unknown loci. In addition, 56 of these loci were specifically linked to clinically diagnosed Alzheimer’s disease, while several others require further validation. The findings confirm that Alzheimer’s disease is influenced by a highly polygenic architecture, with many genetic variants contributing small effects to overall disease risk. The researchers also detected multiple independent signals within several loci, suggesting complex regulatory mechanisms at play. Importantly, the study shows that many of the identified genetic signals are enriched in biological pathways related to amyloid-β accumulation, tau pathology, lipid metabolism, immune function, and endosomal–lysosomal processes. These pathways are central to current models of Alzheimer’s disease development and progression. Genes associated with these risk loci were found to be highly expressed in microglial cells, the immune cells of the brain. This supports growing evidence that immune responses and neuroinflammation play a crucial role in Alzheimer’s disease.
Genetic risk score predicts disease-related brain pathology
Using the identified loci, the researchers developed a polygenic risk score that captures cumulative genetic risk beyond the well-known APOE gene. Individuals with the highest genetic risk had approximately twice the likelihood of developing severe Alzheimer’s-related brain pathology, including advanced tau tangles and beta-amyloid plaque accumulation, compared to those with average risk. Although the predictive power of the score remains modest, it significantly improves the ability to distinguish individuals at higher risk and may support early identification of those likely to develop Alzheimer’s disease.
Advancing precision medicine in Alzheimer’s disease
Overall, the results provide one of the most comprehensive maps of genetic susceptibility to Alzheimer’s disease to date. The identification of new loci and pathways will support future studies aimed at uncovering molecular mechanisms underlying neurodegeneration, identifying novel drug targets, improving risk prediction and early diagnosis, and developing personalised approaches to treatment and prevention. Further research, particularly in diverse populations and with detailed clinical characterization, will be needed to validate additional loci and better understand their contribution to disease pathology.
For further information, please contact:
Professor Mikko Hiltunen, tel. +358 40 355 2014, mikko.hiltunen (at) uef.fi
University of Eastern Finland, Institute of Biomedicine, Kuopio
Research Director Sami Heikkinen, tel. +358 40 355 3393, sami.heikkinen (at) uef.fi
University of Eastern Finland, Institute of Biomedicine, Kuopio
Research article:
EADB., EADI., Bonn. et al. Consensus meta-analysis of genome-wide association studies for Alzheimer’s disease and related dementias. Nat Genet (2026). https://doi.org/10.1038/s41588-026-02583-1
The research groups are members of the multidisciplinary Neuroscience Research Community (NEURO RC) at the University of Eastern Finland. NEURO RC aims to understand the disease-specific and common molecular mechanisms underlying neurodegenerative diseases and epilepsy and to identify novel biomarkers and therapeutic approaches for their prevention and cure. NEURO RC integrates biological neurosciences with data sciences, neuro-innovations, and neuro-ethics. Learn more and connect with NEURO RC: https://www.uef.fi/en/research-community/neuroscience-neuro
