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Plasma p-tau217 identifies cognitively normal older adults who will develop cognitive impairment in a 10-year window
Yakoub Y, Gonzalez-Ortiz F, Ashton NJ, Déry C, Strikwerda-Brown C, St-Onge F, Ourry V, Schöll M, Geddes MR, Ducharme S, Montembeault M, Rosa-Neto P, et al.. Alzheimer's & Dementia, 2025-02
Topic: Brain proteins, microglia and lab models
Introduction We assessed the prognostic accuracy of plasma p-tau217 in predicting the progression to mild cognitive impairment (MCI) in cognitively unimpaired (CU) individuals over a mean follow-up of 5.65 years after plasma collection (range 1.01-10.47). Methods We included 215 participants from the PREVENT-AD cohort with plasma Aβ 42/40 and p-tau217, 159 with cerebrospinal fluid (CSF) Aβ 42/40 and p-tau217, and 155 with 18 F-NAV4694 and 18 F-flortaucipir PET scans. MCI progression was determined by multidisciplinary consensus among memory experts blind to biomarker and genetic information. Results Cox proportional hazard models indicated a greater progression rate in A+T+ plasma and A-T+ plasma compared to A-T- plasma individuals (HR = 7.81 [95% CI = 3.92 to 15.59] and HR = 4.25 [1.60-11.31] respectively). Similar results were found with CSF (HR = 3.63 [1.72-7.70]) and PET (HR = 9.30 [3.67-23.55]). Discussion Plasma p-tau217 is a prognostic marker for identifying individuals who will develop cognitive impairment within ten years. Highlights Elevated plasma p-tau217 levels in CU individuals indicate future clinical progression. Adding plasma Aβ 42/40 status to p-tau markers did not improve the prediction to MCI. All individuals with abnormal tau PET measured in a temporal meta-ROI progressed to MCI.
Key findings
- Results Cox proportional hazard models indicated a greater progression rate in A+T+ plasma and A-T+ plasma compared to A-T- plasma individuals (HR = 7.81 [95% CI = 3.92 to 15.59] and HR = 4.25 [1.60-11.31] respectively).
- Similar results were found with CSF (HR = 3.63 [1.72-7.70]) and PET (HR = 9.30 [3.67-23.55]).
Why it matters
In cognitively unimpaired individuals followed for a mean of 5.65 years, elevated plasma p-tau217 predicted progression to mild cognitive impairment, with higher rates in those who were also amyloid positive. Adding plasma Aβ42/40 status did not improve prediction, and all individuals with abnormal tau PET in a temporal region progressed to mild cognitive impairment.
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Study details
- Study designcohort
- Participants215
- Effect sizeHR 7.81 (95% CI 3.92-15.59) for progression to MCI with abnormal plasma p-tau217 and Aβ42/40
- Evidence strengthModerate
Limitations
Population was 98% White and 72% female, limiting generalisability; small numbers in the A+T+ and A-T+ groups, and 20% of the reference group also developed MCI, so hazard ratios should be interpreted with caution; part of follow-up occurred during the COVID-19 pandemic.
How this study scored 70/100
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 69 of the 98 points we could judge it on, which is 70 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 215 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 | 4 / 7 | Cited 46 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 15.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 5 / 6 | Cited 29.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 2 / 4 | Cited 46 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Sylvia Villeneuve: h-index 48 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Massachusetts Institute of Technology: institution h-index 2,557 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 16 institution(s) in 6 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40008832) |
| 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 | — |
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Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Yakoub, Y., Gonzalez-Ortiz, F., Ashton, N. J., Déry, C., Strikwerda-Brown, C., St-Onge, F., et al. (2025). Plasma p-tau217 identifies cognitively normal older adults who will develop cognitive impairment in a 10-year window. Alzheimer's & Dementia. https://doi.org/10.1002/alz.14537
Vancouver
Yakoub Y, Gonzalez-Ortiz F, Ashton NJ, Déry C, Strikwerda-Brown C, St-Onge F, et al. Plasma p-tau217 identifies cognitively normal older adults who will develop cognitive impairment in a 10-year window. Alzheimer's & Dementia. 2025. doi:10.1002/alz.14537. PMID: 40008832.
BibTeX
@article{yakoub2025-40008832,
author = {Yakoub, Y. and Gonzalez-Ortiz, F. and Ashton, N. J. and Déry, C. and Strikwerda-Brown, C. and St-Onge, F. and Ourry, V. and Schöll, M. and Geddes, M. R. and Ducharme, S. and Montembeault, M. and Rosa-Neto, P. and others},
title = {{Plasma p-tau217 identifies cognitively normal older adults who will develop cognitive impairment in a 10-year window}},
journal = {Alzheimer's \& Dementia},
year = {2025},
doi = {10.1002/alz.14537},
pmid = {40008832},
url = {https://doi.org/10.1002/alz.14537}
}
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