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Plasma p-tau217 and tau-PET predict future cognitive decline among cognitively unimpaired individuals : implications for clinical trials

Ossenkoppele, Rik LU ; Salvadó, Gemma LU ; Janelidze, Shorena LU ; Pichet Binette, Alexa LU ; Bali, Divya LU ; Karlsson, Linda LU orcid ; Palmqvist, Sebastian LU orcid ; Mattsson-Carlgren, Niklas LU orcid ; Stomrud, Erik LU orcid and Therriault, Joseph , et al. (2025) In Nature Aging 5(5). p.883-896
Abstract

Plasma p-tau217 and tau positron emission tomography (PET) are strong prognostic biomarkers in Alzheimer’s disease (AD), but their relative performance in predicting future cognitive decline among cognitively unimpaired (CU) individuals is unclear. In a head-to-head comparison study including nine cohorts and 1,474 individuals, we show that plasma p-tau217 and medial temporal lobe tau-PET signal display similar associations with cognitive decline on a global cognitive composite test (R2PET = 0.34 versus R2plasma = 0.33, Pdifference = 0.653) and with progression to mild cognitive impairment (hazard ratio (HR)PET = 1.61 (1.48–1.76) versus HRplasma = 1.57... (More)

Plasma p-tau217 and tau positron emission tomography (PET) are strong prognostic biomarkers in Alzheimer’s disease (AD), but their relative performance in predicting future cognitive decline among cognitively unimpaired (CU) individuals is unclear. In a head-to-head comparison study including nine cohorts and 1,474 individuals, we show that plasma p-tau217 and medial temporal lobe tau-PET signal display similar associations with cognitive decline on a global cognitive composite test (R2PET = 0.34 versus R2plasma = 0.33, Pdifference = 0.653) and with progression to mild cognitive impairment (hazard ratio (HR)PET = 1.61 (1.48–1.76) versus HRplasma = 1.57 (1.43–1.72), Pdifference = 0.322). Combined plasma and PET models were superior to the single-biomarker models (R2 = 0.35, P < 0.01). Sequential selection using plasma phosphorylated tau at threonine 217 (p-tau217) and then tau-PET reduced the number of participants required for a clinical trial by 94%, compared to a 76% reduction when using plasma p-tau217 alone. Thus, plasma p-tau217 and tau-PET showed similar performance for predicting future cognitive decline in CU individuals, and their sequential use enhances screening efficiency for preclinical AD trials.

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author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Aging
volume
5
issue
5
article number
2311
pages
14 pages
publisher
Springer
external identifiers
  • scopus:105002026271
  • pmid:40155777
DOI
10.1038/s43587-025-00835-z
language
English
LU publication?
yes
id
108a9e1c-7fad-4d63-ab0b-3b7125920a45
date added to LUP
2025-09-03 10:57:36
date last changed
2025-10-01 13:39:48
@article{108a9e1c-7fad-4d63-ab0b-3b7125920a45,
  abstract     = {{<p>Plasma p-tau217 and tau positron emission tomography (PET) are strong prognostic biomarkers in Alzheimer’s disease (AD), but their relative performance in predicting future cognitive decline among cognitively unimpaired (CU) individuals is unclear. In a head-to-head comparison study including nine cohorts and 1,474 individuals, we show that plasma p-tau217 and medial temporal lobe tau-PET signal display similar associations with cognitive decline on a global cognitive composite test (R<sup>2</sup><sub>PET</sub> = 0.34 versus R<sup>2</sup><sub>plasma</sub> = 0.33, P<sub>difference</sub> = 0.653) and with progression to mild cognitive impairment (hazard ratio (HR)<sub>PET</sub> = 1.61 (1.48–1.76) versus HR<sub>plasma</sub> = 1.57 (1.43–1.72), P<sub>difference</sub> = 0.322). Combined plasma and PET models were superior to the single-biomarker models (R<sup>2</sup> = 0.35, P &lt; 0.01). Sequential selection using plasma phosphorylated tau at threonine 217 (p-tau217) and then tau-PET reduced the number of participants required for a clinical trial by 94%, compared to a 76% reduction when using plasma p-tau217 alone. Thus, plasma p-tau217 and tau-PET showed similar performance for predicting future cognitive decline in CU individuals, and their sequential use enhances screening efficiency for preclinical AD trials.</p>}},
  author       = {{Ossenkoppele, Rik and Salvadó, Gemma and Janelidze, Shorena and Pichet Binette, Alexa and Bali, Divya and Karlsson, Linda and Palmqvist, Sebastian and Mattsson-Carlgren, Niklas and Stomrud, Erik and Therriault, Joseph and Rahmouni, Nesrine and Rosa-Neto, Pedro and Coomans, Emma M. and van de Giessen, Elsmarieke and van der Flier, Wiesje M. and Teunissen, Charlotte E. and Jonaitis, Erin M. and Johnson, Sterling C. and Villeneuve, Sylvia and Benzinger, Tammie L.S. and Schindler, Suzanne E. and Bateman, Randall J. and Doecke, James D. and Doré, Vincent and Feizpour, Azadeh and Masters, Colin L. and Rowe, Christopher and Wiste, Heather J. and Petersen, Ronald C. and Jack, Clifford R. and Hansson, Oskar}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{883--896}},
  publisher    = {{Springer}},
  series       = {{Nature Aging}},
  title        = {{Plasma p-tau217 and tau-PET predict future cognitive decline among cognitively unimpaired individuals : implications for clinical trials}},
  url          = {{http://dx.doi.org/10.1038/s43587-025-00835-z}},
  doi          = {{10.1038/s43587-025-00835-z}},
  volume       = {{5}},
  year         = {{2025}},
}