Polygenic score integrating neurodegenerative and vascular risk informs dementia risk stratification
iPRS-DEM reflects neurodegenerative and vascular contribution to dementia. We show iPRS-DEM captures additional dementia genetic risk beyond APOE and AD-PRS. iPRS-DEM, in combination with APOE ε4, shows promise for dementia risk stratification. Our results generalize across both population-based and memory-clinic settings. We show transportability of iPRS-DEM to East Asian ancestry.
Authors
- Jean‐Charles Lambert (ORCID: https://orcid.org/0000-0003-0829-7817)
- Aniket Mishra (ORCID: https://orcid.org/0000-0002-8141-1543)
- Catherine Helmer (ORCID: https://orcid.org/0000-0002-5169-7421)
- Hélène Jacqmin‐Gadda (ORCID: https://orcid.org/0000-0002-7727-6625)
- Philippe Amouyel (ORCID: https://orcid.org/0000-0001-9088-234X)
- Cyprien A. Rivier (ORCID: https://orcid.org/0000-0002-1148-1829)
- Yoichiro Kamatani (ORCID: https://orcid.org/0000-0001-8748-5597)
- Aïcha Soumaré (ORCID: https://orcid.org/0000-0002-0178-6506)
- Cécilia Samieri (ORCID: https://orcid.org/0000-0001-9809-7506)
- Tsuyoshi Hachiya (ORCID: https://orcid.org/0000-0002-5274-3266)
- Marie‐Gabrielle Duperron (ORCID: https://orcid.org/0000-0001-7408-7792)
- Guido J. Falcone (ORCID: https://orcid.org/0000-0002-6407-0302)
- Muralidharan Sargurupremraj (ORCID: https://orcid.org/0000-0003-1684-3750)
- Michael Inouye (ORCID: https://orcid.org/0000-0001-9413-6520)
- Jeanne Neuffer (ORCID: https://orcid.org/0000-0002-3667-6948)
- Cécile Proust‐Lima (ORCID: https://orcid.org/0000-0002-9884-955X)
- Santiago Clocchiatti‐Tuozzo (ORCID: https://orcid.org/0000-0001-5377-434X)
- David‐Alexandre Trégouët (ORCID: https://orcid.org/0000-0001-9084-7800)
- Stéphanie Debette (ORCID: https://orcid.org/0000-0001-8675-7968)
- Quentin Le Grand (ORCID: https://orcid.org/0000-0002-9299-0747)
- Geneviève Chêne (ORCID: https://orcid.org/0000-0002-8368-6460)
- Vincent Bouteloup (ORCID: https://orcid.org/0009-0008-9956-862X)
- Tim D’Aoust (ORCID: https://orcid.org/0009-0003-5601-1497)
- Carole Dufouil
- M. C. Thibault
- Benjamin Grenier‐Boley (ORCID: https://orcid.org/0009-0004-3412-3997)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Baker Heart and Diabetes Institute (AU)
- Université de Bordeaux (FR)
- Inserm (FR)
- Iwate Medical University (JP)
- Université de Montpellier (FR)
- Université de Lille (FR)
- University of Cambridge (GB)
- Institut Pasteur de Lille (FR)
- Centre Hospitalier Universitaire de Bordeaux (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- Yale University (US)
- Sorbonne Université (FR)
- Institut des Maladies Neurodégénératives (FR)
- Bridge University (SS)
- Bordeaux Population Health (FR)
- Institute for Neurodegenerative Disorders (US)
- Yale New Haven Health System (US)
- Institute for Neurosciences of Montpellier (FR)
- Tohoku Medical Megabank Organization (JP)
- Institut du Cerveau (FR)
- The University of Tokyo (JP)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2025-03-01
- DOI
- https://doi.org/10.1002/alz.70014
- Citations
- 7
- Primary Topic
- Dementia and Cognitive Impairment Research
- Type
- article
- Field-Weighted Citation Impact
- 10.30
Funders
- European Commission
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Fondation pour la Recherche Médicale
- Fondation de France
- Fondation Plan Alzheimer
- Mutuelle Générale de l'Education Nationale
- Fondation Claude Pompidou
- National Institutes of Health