Plasma phosphorylated tau 217 and longitudinal trajectories of Aβ, tau, and cognition in cognitively unimpaired older adults
Plasma phosphorylated tau 217 (pTau217) is an excellent biomarker of Alzheimer's disease (AD) pathology, but it remains uncertain whether pTau217 can predict amyloid-β (Aβ) and tau accumulation prior to Aβ positron emission tomography (PET) positivity. Here, we leverage data from a well-characterized prospective cohort of cognitively unimpaired older adults to examine mass spectrometry-based plasma %pTau217 (pTau217/non-phosphorylated-Tau217×100) relative to changes in Aβ/tau PET and cognition. A higher baseline %pTau217 was associated with faster Aβ and tau accumulation on PET, which then led to greater cognitive decline. Among individuals Aβ PET-negative at baseline, higher %pTau217 levels presaged increases in Aβ and tau PET signals. Together, our results suggest that very low %pTau217 in cognitively unimpaired older adults is associated with a minimal risk of AD pathology accumulation and cognitive decline.
Authors
- Heidi I.L. Jacobs (ORCID: https://orcid.org/0000-0001-7620-3822)
- Reisa Anne Sperling (ORCID: https://orcid.org/0000-0003-1535-6133)
- Philip B. Verghese (ORCID: https://orcid.org/0000-0003-4793-564X)
- Juliana A. U. Anzai
- Rachel F. Buckley (ORCID: https://orcid.org/0000-0002-5356-5537)
- Wai‐Ying Wendy Yau (ORCID: https://orcid.org/0000-0002-7597-7647)
- Joel B. Braunstein (ORCID: https://orcid.org/0000-0002-1155-0206)
- M. Farrell (ORCID: https://orcid.org/0000-0002-2706-3218)
- Michael J Properzi (ORCID: https://orcid.org/0000-0001-7855-2372)
- Dennis J. Selkoe (ORCID: https://orcid.org/0000-0001-8846-9767)
- Jasmeer P. Chhatwal (ORCID: https://orcid.org/0000-0002-7792-1698)
- H Y Yang
- Andrea M. Román Viera
- Lei Liu (ORCID: https://orcid.org/0000-0002-4604-4629)
- Courtney Maa
- Dylan Kirn
- Aaron P. Schultz
- Gad A. Marshall
- Keith A. Johnson
- Rebecca E. Amariglio
- Dorene M. Rentz
- Kathryn V. Papp
- Brian C. Healy
- Jean-Pierre Bellier
Institutions
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- Harvard University (US)
- The University of Melbourne (AU)
- Massachusetts General Hospital (US)
- C2N Diagnostics (United States) (US)
- Australian Psychological Society (AU)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-04-14
- DOI
- https://doi.org/10.1038/s41467-026-71269-3
- Primary Topic
- Dementia and Cognitive Impairment Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Massachusetts General Hospital
- Centre d'Imagerie BioMédicale
- National Institutes of Health
- Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital
- National Institute of Biomedical Imaging and Bioengineering