TY - JOUR
T1 - Plasma p-tau217 and tau-PET predict future cognitive decline among cognitively unimpaired individuals
T2 - implications for clinical trials
AU - Ossenkoppele, Rik
AU - Salvadó, Gemma
AU - Janelidze, Shorena
AU - Pichet Binette, Alexa
AU - Bali, Divya
AU - Karlsson, Linda
AU - Palmqvist, Sebastian
AU - Mattsson-Carlgren, Niklas
AU - Stomrud, Erik
AU - Therriault, Joseph
AU - Rahmouni, Nesrine
AU - Rosa-Neto, Pedro
AU - Coomans, Emma M.
AU - van de Giessen, Elsmarieke
AU - van der Flier, Wiesje M.
AU - Teunissen, Charlotte E.
AU - Jonaitis, Erin M.
AU - Johnson, Sterling C.
AU - Villeneuve, Sylvia
AU - Benzinger, Tammie L. S.
AU - Schindler, Suzanne E.
AU - Bateman, Randall J.
AU - Doecke, James D.
AU - Doré, Vincent
AU - Feizpour, Azadeh
AU - Masters, Colin L.
AU - Rowe, Christopher
AU - Wiste, Heather J.
AU - Petersen, Ronald C.
AU - PREVENT-AD Research Group
AU - Jack, Clifford R.
AU - Hansson, Oskar
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/5
Y1 - 2025/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=105002026271&partnerID=8YFLogxK
U2 - 10.1038/s43587-025-00835-z
DO - 10.1038/s43587-025-00835-z
M3 - Article
C2 - 40155777
SN - 2662-8465
VL - 5
SP - 883
EP - 896
JO - Nature Aging
JF - Nature Aging
IS - 5
M1 - 2311
ER -