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Predicting onset of symptomatic Alzheimer's disease with plasma p-tau217 clocks
Kellen K Petersen, Marta Milà-Alomà, Yan Li, Lianlian Du, Chengjie Xiong, Duygu Tosun, Benjamin Saef, Ziad S Saad, et al.. Nature medicine, 2026-02-19
Topic: Amyloid, tau and blood-test diagnosis
Predicting not just if, but also when, cognitively unimpaired individuals are likely to develop onset of Alzheimer's disease (AD) symptoms would be useful to clinical trials and, eventually, clinical practice. Although clock models based on amyloid and tau positron emission tomography have shown promise in predicting the onset of AD symptoms, a model based on plasma biomarkers would be more accessible. Using longitudinal plasma %p-tau217 (the ratio of phosphorylated to non-phosphorylated tau at position 217) from two independent cohorts (n = 258 and n = 345), clock models were used to estimate the age at plasma %p-tau217 positivity. The estimated age at plasma %p-tau217 positivity was associated with the age at onset of AD symptoms (adjusted R 2 of 0.337-0.612) with a median absolute error of 3.0-3.7 years. Notably, the time from %p-tau217 positivity to onset of AD symptoms was markedly shorter in older individuals. Similar models were constructed with data from one p-tau217/Aβ42 immunoassay and four plasma p-tau217 immunoassays. These findings suggest that the time until onset of AD symptoms can be estimated using a single blood test within a margin of error that is acceptable for use in clinical trials.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Petersen, K. K., Milà-Alomà, M., Li, Y., Du, L., Xiong, C., Tosun, D., et al. (2026). Predicting onset of symptomatic Alzheimer's disease with plasma p-tau217 clocks. Nature medicine. https://doi.org/10.1038/s41591-026-04206-y
Vancouver
Petersen KK, Milà-Alomà M, Li Y, Du L, Xiong C, Tosun D, et al. Predicting onset of symptomatic Alzheimer's disease with plasma p-tau217 clocks. Nature medicine. 2026. doi:10.1038/s41591-026-04206-y. PMID: 41714746.
BibTeX
@article{petersen2026-41714746,
author = {Petersen, Kellen K and Milà-Alomà, Marta and Li, Yan and Du, Lianlian and Xiong, Chengjie and Tosun, Duygu and Saef, Benjamin and Saad, Ziad S and others},
title = {{Predicting onset of symptomatic Alzheimer's disease with plasma p-tau217 clocks}},
journal = {Nature medicine},
year = {2026},
doi = {10.1038/s41591-026-04206-y},
pmid = {41714746},
url = {https://doi.org/10.1038/s41591-026-04206-y}
}
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Key findings
- The estimated age at plasma %p-tau217 positivity was associated with the age at onset of AD symptoms (adjusted R 2 of 0.337-0.612) with a median absolute error of 3.0-3.7 years.
- These findings suggest that the time until onset of AD symptoms can be estimated using a single blood test within a margin of error that is acceptable for use in clinical trials.
Why it matters
Using repeated blood tests for a tau marker, this study estimated the age at which a person would first test positive and linked it to the age when Alzheimer's symptoms began, with a median error of about 3 to 3.7 years. The authors suggest this single blood test approach could be useful for clinical trials, though it is not yet a clinical tool.
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Study details
- Study designcohort
- Participants603
- Effect sizeAdjusted R2 0.337-0.612 for predicting age at symptom onset; median absolute error 3.0-3.7 years
- Evidence strengthModerate
Limitations
Two research cohorts of volunteers, not community samples; the clocks are calibrated to symptom onset in those cohorts and need external validation; the error margin is too wide for individual prediction.
How this study scored 70/100
Published in a top-tier journal, and it is a cohort study following people over time. Scored zero for randomized / blinded because the record does not state it. We have no data on free to read, so that was left out: it earned 69 of the 98 points we could judge it on, which is 70 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature medicine) |
| Journal's citation record | 4 / 4 | Nature Medicine: journal h-index 763 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 603 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 37 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 18.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 6 / 6 | Cited 169.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 2 / 4 | Cited 37 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 0 / 4 | Last-listed author Alzheimer's Disease Neuroimaging Initiative (ADNI): h-index 4 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multicenter collaboration | 3 / 3 | OpenAlex lists 23 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41714746) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 69 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 69 of the 98 points we could judge it on is 70 out of 100. |
| Total | 70 / 100 | — |
What each of these 20 components measures, and what this score is not →
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