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Plasma Phosphorylated Tau 217 to Identify Preclinical Alzheimer Disease
Salvadó G, Janelidze S, Bali D, Dolado AO, Therriault J, Brum WS, Pichet Binette A, Stomrud E, Mattsson-Carlgren N, Palmqvist S, Coomans EM, Teunissen CE, et al.. JAMA Neurology, 2025-11-01
Topic: Amyloid, tau and blood-test diagnosis
Importance Advances in Alzheimer disease (AD) have shifted research focus to earlier disease stages, necessitating more scalable approaches to identify cognitively unimpaired individuals with amyloid β (Aβ) pathology. Objective To assess the utility of plasma phosphorylated tau 217 (p-tau217) for classifying Aβ status in cognitively unimpaired individuals, both as a stand-alone test and in a 2-step approach where positive plasma results were confirmed using a second modality (Aβ positron emission tomography [PET] or cerebrospinal fluid [CSF]). Design, setting, and participants This cross-sectional cohort study used data collected between June 2009 and March 2024. We included 2916 cognitively unimpaired participants from 12 international independent observational cohorts in the US, Europe, Australia, and Canada with available plasma p-tau217 levels and CSF or PET Aβ biomarkers. Performance comparisons between mass spectrometry and immunoassay-based p-tau217 measurements were also performed (n = 964). Exposures Plasma p-tau217 levels measured by immunoassay. Main outcome and measures Aβ status, determined by CSF or Aβ PET biomarkers. Results Participants had a mean (SD) age of 66.9 (9.9) years; 971 (33.3%) were Aβ positive by either CSF or PET, 1667 (57.2%) were women, and 1108 (38.1%) carried at least 1 APOE ε4 allele. As a stand-alone test, plasma p-tau217 achieved a positive predictive value (PPV) of 79% (95% CI, 74-84) and an overall accuracy of 81% (95% CI, 80-82). In a 2-step workflow, the PPV and accuracy significantly increased to 91% (95% CI, 86-95). While this approach required screening of 677 individuals with plasma p-tau217 to identify 100 Aβ-positive individuals, compared to 536 participants when using PET alone, it reduced the need for PET testing to 124. Immunoassays demonstrated comparable PPVs to mass spectrometry (80% [95% CI, 74-86] vs 85% [95% CI, 81-90]; P = .12) but significantly lower overall accuracy (82% [95% CI, 79-84]% vs 88 [95% CI, 86-90]; P Conclusions and relevance The findings highlight the potential of plasma p-tau217 as a stand-alone test-or when used in a sequential 2-step approach alongside PET or CSF testing-as a cost-effective, scalable, and minimally burdensome strategy for identifying preclinical AD. Tailored screening workflows that incorporate p-tau217 can improve efficiency in participant selection for preclinical AD trials and, in the future, help guide access to disease-modifying treatments.
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APA 7th
Salvadó, G., Janelidze, S., Bali, D., Dolado, A. O., Therriault, J., Brum, W. S., et al. (2025). Plasma Phosphorylated Tau 217 to Identify Preclinical Alzheimer Disease. JAMA Neurology. https://doi.org/10.1001/jamaneurol.2025.3217
Vancouver
Salvadó G, Janelidze S, Bali D, Dolado AO, Therriault J, Brum WS, et al. Plasma Phosphorylated Tau 217 to Identify Preclinical Alzheimer Disease. JAMA Neurology. 2025. doi:10.1001/jamaneurol.2025.3217. PMID: 40952756.
BibTeX
@article{salvado2025-40952756,
author = {Salvadó, G. and Janelidze, S. and Bali, D. and Dolado, A. O. and Therriault, J. and Brum, W. S. and Pichet Binette, A. and Stomrud, E. and Mattsson-Carlgren, N. and Palmqvist, S. and Coomans, E. M. and Teunissen, C. E. and others},
title = {{Plasma Phosphorylated Tau 217 to Identify Preclinical Alzheimer Disease}},
journal = {JAMA Neurology},
year = {2025},
doi = {10.1001/jamaneurol.2025.3217},
pmid = {40952756},
url = {https://doi.org/10.1001/jamaneurol.2025.3217}
}
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.
Key findings
- Objective To assess the utility of plasma phosphorylated tau 217 (p-tau217) for classifying Aβ status in cognitively unimpaired individuals, both as a stand-alone test and in a 2-step approach where positive plasma results were confirmed using a second modality (Aβ positron emission tomography [PET] or cerebrospinal fluid [CSF]).
- Results Participants had a mean (SD) age of 66.9 (9.9) years; 971 (33.3%) were Aβ positive by either CSF or PET, 1667 (57.2%) were women, and 1108 (38.1%) carried at least 1 APOE ε4 allele.
- As a stand-alone test, plasma p-tau217 achieved a positive predictive value (PPV) of 79% (95% CI, 74-84) and an overall accuracy of 81% (95% CI, 80-82).
- In a 2-step workflow, the PPV and accuracy significantly increased to 91% (95% CI, 86-95).
- While this approach required screening of 677 individuals with plasma p-tau217 to identify 100 Aβ-positive individuals, compared to 536 participants when using PET alone, it reduced the need for PET testing to 124.
Why it matters
In 2,916 cognitively unimpaired participants, plasma p-tau217 classified amyloid status both as a stand-alone test and in a two-step approach where positive results were confirmed with PET or cerebrospinal fluid. This supports using blood tests to identify preclinical Alzheimer's disease, though the study was cross-sectional.
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Study details
- Study designcross-sectional
- Participants2,916
- Effect sizeAccuracy 81% stand-alone vs 91% in a two-step workflow; PET scans needed reduced from 536 to 124 per 100 amyloid-positive cases
- Evidence strengthHigh
Limitations
Use of multiple cohorts introduced variability in biomarker measurement despite harmonisation; reliable generalisable cut-offs for plasma p-tau217 are still needed; amyloid prevalence in the sample was slightly higher than in the general cognitively unimpaired population, so validation in more diverse samples is needed.
How this study scored 72/100
Published in a leading specialty journal, and it is a snapshot of people at one point in 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 71 of the 98 points we could judge it on, which is 72 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA Neurology) |
| Journal's citation record | 2 / 4 | JAMA Neurology: journal h-index 235 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in 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 | 2,916 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 64 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 21.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 6 / 6 | Cited 40.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 3 / 4 | Cited 64 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Zaven S. Khachaturian: h-index 56 (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 38 institution(s) in 9 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40952756) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 71 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 71 of the 98 points we could judge it on is 72 out of 100. |
| Total | 72 / 100 | — |
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Read the original
- DOI: 10.1001/jamaneurol.2025.3217
- PubMed: 40952756
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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