The prognostic value of blood-based p-tau217 levels on progression to clinical impairment
Plasma p-tau217 closely tracks amyloid-β (Aβ) pathology, yet its ability to predict long-term clinical progression in cognitively unimpaired (CU) adults remains uncertain. We analyzed harmonized data from 2,705 CU participants (Age<sub>mean</sub>=69.8±7years; Female=63%) across six longitudinal cohorts with up to 13.5 years of follow-up. Cox models evaluated associations between p-tau217 and progression to a clinical diagnosis of cognitive impairment, while natural cubic spline models assessed associations with longitudinal decline on a cognitive composite. Higher p-tau217 was associated with increased risk of progression (hazard-ratio[HR]=1.38; 95%CI:1.31-1.44), independent of demographics and <i>APOE</i>ε4, and in models with Aβ-PET (HR=1.30; 95%CI:1.23-1.38). Very high p-tau217 levels (>2.5SD) were associated with 61%[95%CI:53-68%] absolute risk of progression over 10 years. Elevated p-tau217 associated with accelerated cognitive decline, both independent of, and synergistic with, greater Aβ-PET. These findings establish plasma p-tau217 as a robust prognostic marker in preclinical AD and support its value in future individualized risk prediction.
Authors
- Oliver Langford (ORCID: https://orcid.org/0009-0006-8951-1326)
- Brian C. Healy
- Jorge García Condado (ORCID: https://orcid.org/0000-0002-9463-1924)
- Julie Elisabeth Oomens (ORCID: https://orcid.org/0000-0002-5201-8080)
- Gillian Coughlan (ORCID: https://orcid.org/0000-0003-1806-702X)
- Kathryn V. Papp (ORCID: https://orcid.org/0000-0003-1687-4370)
- Emilie T. Reas (ORCID: https://orcid.org/0000-0002-4110-5154)
- Michael J Properzi (ORCID: https://orcid.org/0000-0001-7855-2372)
- Madison Cuppels
- Maria Carrigan
- Jeff Brown
- J. E. Berg
- Colin Birkenbihl
- Pia Kivisäkk
- Steven D Arnold
- Merle Hönig
- Jasmeer Chhatwal
- Diana L. Townsend
- Keith A. Johnson
- Sid O'Bryant
- Robert A. Rissman
- Paul S. Aisen
- Bryan D. James
- Rebecca E. Amariglio
- Annie Li
- Aaron P. Schultz
- Michael Donohue
- Reisa A. Sperling
- Wai-Ying (Wendy) Yau
- Hyun-Sik Yang
- Timothy J. Hohman
- Mabel T. Seto
- Sterling C. Johnson
- Melissa Petersen
- Michelle Farrell
- Dorene M. Rentz
Institutions
- University of Southern California (US)
- University of North Texas (US)
- Rush University Medical Center (US)
- University of Wisconsin–Madison (US)
- University of North Texas Health Science Center (US)
- The University of Melbourne (AU)
- Forschungszentrum Jülich (DE)
- Amsterdam University Medical Centers (NL)
- Mass General Brigham (US)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- medRxiv
- Published
- 2026-02-09
- DOI
- https://doi.org/10.64898/2026.02.06.26345770
- Primary Topic
- Dementia and Cognitive Impairment Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00