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An International Working Group viewpoint on stratifying risk and prevention of the clinical expression of Alzheimer’s disease

Nature Aging volume 5, pages 1930–1932 (2025)Cite this article

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Biofluid and imaging biomarkers for Alzheimer’s disease can identify disease pathology in cognitively unimpaired people, a substantial proportion of whom will not clinically express the disease. The International Working Group offers a risk stratification framework for management directed at the prevention of the clinical expression of Alzheimer’s disease.

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Fig. 1: Risk classification for clinical expression of Alzheimer’s disease.

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Acknowledgements

The authors gratefully acknowledge the contributions of the members of the IWG to the progress in advancing these diagnostic criteria for Alzheimer’s disease from 2007 to present. H.H.F. is grateful for the support the Epstein Family Chancellor’s Endowed Chair in Alzheimer’s Disease Research at UC San Diego.

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Authors and Affiliations

  1. Alzheimer’s Disease Cooperative Study, University of California San Diego, School of Medicine, La Jolla, CA, USA

    Howard H. Feldman

  2. Department of Neurosciences, University of California San Diego, La Jolla, CA, USA

    Howard H. Feldman

  3. Sorbonne Université, INSERM U1127, CNRS 7225, Institut du Cerveau - ICM, Paris, France

    Nicolas Villain & Bruno Dubois

  4. AP-HP Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Neurology, Institute of Memory and Alzheimer’s Disease, Paris, France

    Nicolas Villain & Bruno Dubois

  5. UniGE, Geneva, Switzerland

    Giovanni B. Frisoni

Authors
  1. Howard H. Feldman
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  2. Nicolas Villain
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  3. Giovanni B. Frisoni
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  4. Bruno Dubois
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Contributions

H.H.F., N.V., G.B.F. and B.D. contributed to the conceptualization and drafting as well as editing of this Comment. All authors approved the final submitted version.

Corresponding author

Correspondence to Howard H. Feldman.

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Competing interests

Independent of this work, H.H.F. discloses grant funding from Allyx Pharmaceuticals, Vivoryon (Probiodrug), Biohaven Pharmaceuticals and LuMind Foundation; service agreements for consulting activities with LuMind Foundation, Axon Neuroscience, Novo Nordisk, Arrowhead Pharmaceuticals, Biosplice Therapeutics, Roche/Genentech Pharmaceuticals (DMC/DSMB), Tau Consortium (SAB) and Janssen Research & Development (DSMB); support for travel from Novo Nordisk, Royal Society of Canada, Translating Research in Elder Care (TREC), Association for Frontotemporal Dementia (AFTD) and Rainwater Charitable Foundation; and a philanthropic donation for the Epstein Family Alzheimer Research Collaboration. For these activities, no personal funds have been received with all payments to UC San Diego. H.H.F. personally receives royalties for patent: Feldman HH (filed November 26, 2008). Detecting and Treating Dementia Serial Number 12/3-2691 US Patent No. PCT/US2007/07008. Washington, DC: US Patent and Trademark Office. N.V. received research support from Fondation Bettencourt-Schueller, Fondation Servier, Union Nationale pour les Intérêts de la Médecine (UNIM), Fondation Claude Pompidou, Fondation Alzheimer, Banque Publique d’Investissement, Lion’s Club Alzheimer and Fondation pour la Recherche sur l’Alzheimer; travel grants from the Movement Disorders Society, Merz-Pharma, UCB Pharma, and GE Healthcare SAS; is an unpaid local principal investigator or subinvestigator in NCT05531526 (AR1001, AriBio), NCT06079190 (AL101, GSK), NCT04241068 and NCT05310071 (aducanumab, Biogen), NCT05399888 (BIIB080, Biogen), NCT03352557 (gosuranemab, Biogen), NCT04592341 (gantenerumab, Roche), NCT03887455 (lecanemab, Eisai), NCT03828747 and NCT03289143 (semorinemab, Roche), NCT04619420 (JNJ-63733657, Janssen – Johnson & Johnson), NCT04374136 (AL001, Alector), NCT04592874 (AL002, Alector), NCT04867616 (bepranemab, UCB Pharma), NCT04777396 and NCT04777409 (semaglutide, Novo Nordisk), and NCT05469360 (NIO752, Novartis); has given unpaid lectures in symposia organized by Eisai and the Servier Foundation; and has been an unpaid expert for Janssen – Johnson & Johnson, Eli-Lilly. G.B.F. has received funding through the Private Foundation of Geneva University Hospitals from: A.P.R.A. – Association Suisse pour la Recherche sur la Maladie d’Alzheimer, Genève; Fondation Segré, Genève; Ivan Pictet, Genève; Race Against Dementia Foundation, London, UK; Fondation Child Care, Genève; Fondation Edmond J. Safra, Genève; Fondation Minkoff, Genève; Fondazione Agusta, Lugano; McCall Macbain Foundation, Canada; Nicole et René Keller, Genève; Fondation AETAS, Genève; has received funding through the University of Geneva or Geneva University Hospitals: for IISSs from ROCHE Pharmaceuticals OM Pharma EISAI Pharmaceuticals Biogen Pharmaceuticals and Novo Nordisk; has received funding for competitive research projects from: H2020, Innovative Medicines Initiative (IMI), IMI2, Swiss National Science Foundation, and VELUX Foundation; has received consulting fees from: Biogen, Diadem, Roche; and has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from: Biogen, Roche, Novo Nordisk, GE HealthCare. B.D. received research support from for his institution from Fondation Merck-Avenir, Fondation des Gueules Cassées, Fondation Recherche Alzheimer, Lions Club Alzheimer and Roche. B.D. received consulting fees from Qynapse, Biogen, ABscience and Janssen.

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Feldman, H.H., Villain, N., Frisoni, G.B. et al. An International Working Group viewpoint on stratifying risk and prevention of the clinical expression of Alzheimer’s disease. Nat Aging 5, 1930–1932 (2025). https://doi.org/10.1038/s43587-025-00977-0

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