Tau biology, biomarkers, and therapeutics

  • Alzheimers Dement (N Y). 2025 Oct 21;11(4):e70165. doi: 10.1002/trc2.70165.
Bess Frost  1 ,  Hartmuth Kolb  2 ,  Alicia Algeciras-Schimnich  3 ,  Tobey J Betthauser  4  5 ,  Sarah DeVos  6 ,  Rebecca M Edelmayer  7 ,  Fiona Elwood  8 ,  Adam S Fleisher  9 ,  David Henley  10 ,  Kanta Horie  11 ,  Bradley Hyman  12 ,  William Charles Kreisl  13 ,  Luka Kulic  14  15 ,  Antoine Leuzy  2  16 ,  Jose-Alberto Palma  9 ,  Sophie Parmentier-Batteur  17 ,  Maria-Magdalena Patru  18 ,  Gil D Rabinovici  19  20 ,  Larisa Reyderman  13 ,  Reisa A Sperling  21  22 ,  Serge Van Der Geyten  21 ,  Kristin R Wildsmith  11 ,  Simin Mahinrad  7 ,  Maria C Carrillo  7 ,  Christopher J Weber  7
Affiliations
  • 1. Center for Alzheimer's Disease Research Department of Molecular Biology Cellular Biology and Biochemistry Brown University Providence Rhode Island USA.
  • 2. Enigma Biomedical Group Knoxville Tennessee USA.
  • 3. Department of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota USA.
  • 4. Wisconsin Alzheimer's Disease Research Center University of Wisconsin School of Medicine and Public Health Madison Wisconsin USA.
  • 5. Department of Medicine University of Wisconsin School of Medicine and Public Health Madison Wisconsin USA.
  • 6. Curie.Bio. Boston Massachusetts USA.
  • 7. Alzheimer's Association Chicago Illinois USA.
  • 8. Johnson & Johnson Cambridge Massachusetts USA.
  • 9. Neurodegeneration Early Phase Eli Lilly & Co. Lilly Corporate Center Indianapolis Indiana USA.
  • 10. Johnson and Johnson Titusville New Jersey USA.
  • 11. Deep Human Biology Learning (DHBL) Eisai Inc. Nutley New Jersey USA.
  • 12. Department of Neurology Massachusetts General Hospital Boston Massachusetts USA.
  • 13. Clinical Research Eisai Inc Nutley New Jersey USA.
  • 14. F. Hoffmann-La Roche Ltd Basel Switzerland.
  • 15. Critical Path for Alzheimer's Disease (CPAD) Consortium Critical Path Institute Tucson Arizona USA.
  • 16. Novartis Institutes for Biomedical Research Cambridge Massachusetts USA.
  • 17. Medical and Scientific Affairs Roche Diagnostics Corporation Indianapolis Indiana USA.
  • 18. Department of Neurology and Department of Radiology and Biomedical Imaging University of California San Francisco San Francisco California USA.
  • 19. Department of Radiology and Biomedical Imaging University of California San Francisco San Francisco California USA.
  • 20. Department of Neurology Brigham and Women's Hospital Harvard Medical School Boston Massachusetts USA.
  • 21. Department of Neurology Massachusetts General Hospital Harvard Medical School Boston Massachusetts USA.
  • 22. Johnson & Johnson Beerse Belgium.
PMID: 41126950 DOI: 10.1002/trc2.70165
Abstract

As Alzheimer's disease (AD) research advances, tau has emerged as both a critical biomarker and a promising therapeutic target, central to understanding disease mechanisms, tracking progression, and guiding treatment development. The Fall 2024 Alzheimer's Association Research Roundtable convened experts from academia, industry, National Institutes of Health (NIH), and the United States Food and Drug Administration (FDA) to explore current progress and future directions in tau-centered diagnostics and therapeutics. Discussions addressed the integration of tau biomarkers into the 2024 Revised Diagnostic Criteria for AD, updates to amyloid and tau positron emission tomography (PET) imaging, and modeling of biomarker trajectories. Presenters highlighted tau-targeting therapeutics including Antisense Oligonucleotides, monoclonal antibodies, and small molecules, alongside innovations in drug delivery. The interplay between anti-amyloid and anti-tau therapies and strategic design of combination trials were key themes. Regulatory insights facilitated discussions on drug approval pathways. The meeting highlighted the rapid evolution of tau research and emphasized opportunities to improve diagnostics, trial design, and treatment strategies in AD.

Highlights: The Alzheimer's Association Research Roundtable (AARR) convened leaders from industry, academia, and government, to explore current progress and future directions in tau-centered diagnostics and therapeutics.Tau has emerged as both a critical biomarker and a promising therapeutic target, central to understanding disease mechanisms, tracking progression, and guiding treatment development.Discussions addressed the integration of tau biomarkers into the 2024 revised diagnostic criteria for AD, updates to amyloid and tau PET imaging, modeling of biomarker trajectories, tau-targeting therapeutics, and interplay between anti-amyloid and anti-tau therapies and strategic design of combination trials.

Keywords
AUC; Alzheimer's disease staging; Alzheimer's disease treatments; PET imaging; amyloid; biomarker; clinical trials; combination therapy; tau.
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