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Plasma p-tau217 and tau-PET predict future cognitive decline among cognitively unimpaired individuals: implications for clinical trials
Ossenkoppele R, Salvadó G, Janelidze S, Pichet Binette A, Bali D, Karlsson L, Palmqvist S, Mattsson-Carlgren N, Stomrud E, Therriault J, Rahmouni N, Rosa-Neto P, et al.. Nature Aging, 2025-03-28
Topic: Brain proteins, microglia and lab models
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 2 PET = 0.34 versus R 2 plasma = 0.33, P difference = 0.653) and with progression to mild cognitive impairment (hazard ratio (HR) PET = 1.61 (1.48-1.76) versus HR plasma = 1.57 (1.43-1.72), P difference = 0.322). Combined plasma and PET models were superior to the single-biomarker models (R 2 = 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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APA 7th
Ossenkoppele, R., Salvadó, G., Janelidze, S., Pichet Binette, A., Bali, D., Karlsson, L., et al. (2025). Plasma p-tau217 and tau-PET predict future cognitive decline among cognitively unimpaired individuals: implications for clinical trials. Nature Aging. https://doi.org/10.1038/s43587-025-00835-z
Vancouver
Ossenkoppele R, Salvadó G, Janelidze S, Pichet Binette A, Bali D, Karlsson L, et al. Plasma p-tau217 and tau-PET predict future cognitive decline among cognitively unimpaired individuals: implications for clinical trials. Nature Aging. 2025. doi:10.1038/s43587-025-00835-z. PMID: 40155777.
BibTeX
@article{ossenkoppele2025-40155777,
author = {Ossenkoppele, R. and Salvadó, G. and Janelidze, S. and Pichet Binette, A. and Bali, D. and Karlsson, L. and Palmqvist, S. and Mattsson-Carlgren, N. and Stomrud, E. and Therriault, J. and Rahmouni, N. and Rosa-Neto, P. and others},
title = {{Plasma p-tau217 and tau-PET predict future cognitive decline among cognitively unimpaired individuals: implications for clinical trials}},
journal = {Nature Aging},
year = {2025},
doi = {10.1038/s43587-025-00835-z},
pmid = {40155777},
url = {https://doi.org/10.1038/s43587-025-00835-z}
}
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Key findings
- 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 2 PET = 0.34 versus R 2 plasma = 0.33, P difference = 0.653) and with progression to mild cognitive impairment (hazard ratio (HR) PET = 1.61 (1.48-1.76) versus HR plasma = 1.57 (1.43-1.72), P difference = 0.322).
- 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.
Why it matters
Plasma p-tau217 and tau-PET performed similarly in predicting future cognitive decline among cognitively unimpaired individuals, and combining them was slightly better than either alone. Using plasma p-tau217 first and then tau-PET reduced the number of participants needed for a clinical trial by 94%, which could make preclinical Alzheimer's trials more efficient.
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Study details
- Study designcohort
- Participants1,474
- Effect sizeHR for progression to MCI 1.57 (plasma p-tau217) vs 1.61 (tau PET) per unit; 94% reduction in trial screening with sequential use
- Evidence strengthHigh
Limitations
Multicentre study not co-designed from the start: p-tau217 cut-offs were not available from all cohorts so z-scores or quartiles were used; residual heterogeneity from different PET tracers, p-tau217 assays and neuropsychological tests; tau PET was more often analysed locally while plasma was analysed centrally; the authors call for larger studies with predefined cut-offs in more diverse populations.
How this study scored 79/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for randomised / blinded because the record does not state it. We have no data on free to read, so that was left out: it earned 77 of the 98 points we could judge it on, which is 79 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature Aging) |
| Journal's citation record | 1 / 4 | Nature Aging: journal h-index 103 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,474 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 100 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 33.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 6 / 6 | Cited 63.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 16 other studies in this library |
| Still being cited | 3 / 4 | Cited 100 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Oskar Hansson: h-index 148 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 16 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40155777) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 77 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 77 of the 98 points we could judge it on is 79 out of 100. |
| Total | 79 / 100 | — |
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