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  • Perspective
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Towards pharmacological prevention of Alzheimer disease

Nature Reviews Neurology volume 21, pages 721–733 (2025)Cite this article

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Abstract

Prevention of Alzheimer disease (AD) is a medical challenge owing to its complex pathogenesis, which involves amyloid-β (Aβ) and tau aggregation, neuroinflammation and progressive neurodegeneration. Development of disease-specific biomarkers has transformed our ability to detect AD pathology early, enabling more accurate diagnosis, monitoring and the development of targeted disease-modifying therapies. Consequently, primary and secondary prevention of AD have become feasible goals. In this Perspective, we examine current and emerging pharmacological strategies for the prevention of AD, particularly the use of existing anti-Aβ therapies and emerging anti-tau approaches, among people at risk of AD or in the earliest, presymptomatic stages of the disease. We highlight the key challenges in implementing prevention trials, discuss ongoing prevention trials and their implications, and consider the potential and challenges of translation into clinical practice. Implementation of preventative strategies, supported by biomarker-guided patient selection and innovative trial designs, has the potential to substantially delay or prevent the cognitive decline caused by AD. Success would fundamentally transform the AD therapeutic landscape, reducing the socioeconomic burden of dementia and preserving cognitive function in ageing populations worldwide.

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Fig. 1: Timeline of major milestones in Alzheimer disease research, diagnosis and treatment.
Fig. 2: Changes in core Alzheimer disease biomarkers in relation to clinical onset.
Fig. 3: Interventional framework for Alzheimer disease prevention.
Fig. 4: Historical precedent for prevention in a dominantly inherited disease.
Fig. 5: Alzheimer disease core pathology and pharmacological approaches to prevention.

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Acknowledgements

The authors thank all study participants and their families, whose commitment makes prevention research in Alzheimer disease possible.

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Authors and Affiliations

  1. Washington University School of Medicine, St Louis, MO, USA

    Jorge J. Llibre-Guerra, Eric M. McDade, Suzanne E. Schindler, David B. Clifford, Charlene Supnet & Randall J. Bateman

  2. Banner Alzheimer’s Institute, Sun City and Phoenix, AZ, USA

    Alireza Atri

  3. Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Alireza Atri

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  1. Jorge J. Llibre-Guerra
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  2. Eric M. McDade
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  6. Alireza Atri
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  7. Randall J. Bateman
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J.J.L.-G. researched data for the article. All authors contributed substantially to discussion of the content, wrote the article, and reviewed and/or edited the manuscript before submission.

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Correspondence to Jorge J. Llibre-Guerra or Randall J. Bateman.

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J.J.L.-G.’s research is supported by the National Institutes of Health National Institute of Aging (K01AG073526), the Alzheimer’s Association (AARFD-21-851415, SG-20-690363, 24HPE-1287320), the Michael J. Fox Foundation (MJFF-020770) and The Foundation for Barnes–Jewish Hospital. E.M.McD. has received research funding from the Alzheimer’s Association, Eisai, Eli Lilly, GHR, Hoffman–La Roche, and the National Institutes of Health. E.M.McD. has served as a consultant or adviser for Alzamend, AstraZeneca, Hoffman–La Roche, Ionis and Sanofi. E.M.McD. has served as a data and safety monitoring board member for Alector and Alnylum, and is on the scientific advisory board for Foundation Alzheimer. S.E.S. has served on scientific advisory boards related to biomarker testing and education for companies including Eisai, Eli Lilly and Novo Nordisk. D.B.C. receives royalties from Wolters Kluwer. D.B.C. serves as scientific consultant to Atara Biotherapeutics, Cellevolve Bio, Excision BioTherapeutics, F. Hoffmann–La Roche/Genentech, ICON (Teva), Sanofi Genzyme, Seagen and Wave Life Sciences. D.B.C. has carried out legal consulting for Lewis, Thomason, King, Krieg and Waldrop and Loughren, Loughren, Loughren Powell Gilbert. D.B.C. serves on the data safety monitoring boards for Atara Biotherapeutics, Avidity, Cellevolve Bio, Excision Biotherapeutics, Morphic, Sanofi Genzyme, Teva and Wave Life Sciences. A.A. has received consulting fees from multiple pharmaceutical and biotechnology companies, including Eisai, Lundbeck, Merck, Novo Nordisk, Prothena and Roche/Genentech. A.A.’s institution receives grant and research support from the National Institutes of Health (NIH), the State of Arizona, Gates Ventures and several industry partners. R.J.B. receives laboratory research funding from the Alzheimer’s Association, Association for Frontotemporal Degeneration, Association for Frontotemporal Degeneration FTD Biomarkers Initiative, Avid Radiopharmaceuticals, BrightFocus Foundation, Centene Corporation, Coins for Alzheimer’s Research Trust Fund, the Cure Alzheimer’s Fund, DIAN-TU Pharma Consortium, Good Ventures Foundation, Janssen, the National Institutes of Health, the NfL Consortium (AbbVie, Biogen, Bristol Meyers Squibb, Hoffman La Roche), Novartis, Rainwater Foundation, Tau Consortium, Tau SILK Consortium (AbbVie, Biogen, Eli Lilly and Company and an anonymous organization), The Foundation for Barnes–Jewish Hospital and the Tracy Family SILQ Center. Washington University and R.J.B. have equity ownership interest in C2N Diagnostics and receive income based on technology (stable isotope labelling kinetics, blood plasma assay, and methods of diagnosing AD with phosphorylation changes) licensed by Washington University to C2N Diagnostics. C.S. declares no financial competing interests.

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Llibre-Guerra, J.J., McDade, E.M., Schindler, S.E. et al. Towards pharmacological prevention of Alzheimer disease. Nat Rev Neurol 21, 721–733 (2025). https://doi.org/10.1038/s41582-025-01154-y

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