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A comprehensive head-to-head comparison of key plasma phosphorylated tau 217 biomarker tests
Warmenhoven N, Salvadó G, Janelidze S, Mattsson-Carlgren N, Bali D, Orduña Dolado A, Kolb H, Triana-Baltzer G, Barthélemy NR, Schindler SE, Aschenbrenner AJ, Raji CA, et al.. Brain, 2025-02-03
Topic: Brain proteins, microglia and lab models
Plasma %p-tau217WashU had the highest performance, with significantly higher AUCs than all the immunoassays (Pdiff < 0.007). Plasma %p-tau217WashU exhibited stronger associations with all PET load outcomes compared with immunoassays; baseline Aβ-PET load (R2: 0.72; immunoassays: 0.47-0.58; Pdiff < 0.001), baseline tau-PET load (R2: 0.51; immunoassays: 0.38-0.45; Pdiff < 0.001), longitudinal Aβ-PET load (R2: 0.53; immunoassays: 0.31-0.38; Pdiff < 0.001) and longitudinal tau-PET load (R2: 0.50; immunoassays: 0.35-0.43; Pdiff < 0.014). Among immunoassays, plasma p-tau217Lilly was more associated with Aβ-PET load than plasma p-tau217Janssen (Pdiff < 0.020) and with tau-PET load than both plasma p-tau217Janssen and plasma p-tau217ALZpath (all Pdiff < 0.010). The main results were replicated in an external cohort from Washington University in St Louis (n = 219). In summary, both mass spectrometry- and immunoassay-based p-tau217 tests generally perform well in identifying Aβ-PET, tau-PET and cognitive abnormalities, but %p-tau217WashU performed significantly better than all the examined immunoassays. Plasma %p-tau217 may be considered as a stand-alone confirmatory test for Alzheimer's disease pathology, whereas some immunoassays might be better suited as triage tests where positive results are confirmed with a second test, which needs to be determined by future reviews incorporating results from multiple cohorts.
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APA 7th
Warmenhoven, N., Salvadó, G., Janelidze, S., Mattsson-Carlgren, N., Bali, D., Orduña Dolado, A., et al. (2025). A comprehensive head-to-head comparison of key plasma phosphorylated tau 217 biomarker tests. Brain. https://doi.org/10.1093/brain/awae346
Vancouver
Warmenhoven N, Salvadó G, Janelidze S, Mattsson-Carlgren N, Bali D, Orduña Dolado A, et al. A comprehensive head-to-head comparison of key plasma phosphorylated tau 217 biomarker tests. Brain. 2025. doi:10.1093/brain/awae346. PMID: 39468767.
BibTeX
@article{warmenhoven2025-39468767,
author = {Warmenhoven, N. and Salvadó, G. and Janelidze, S. and Mattsson-Carlgren, N. and Bali, D. and Orduña Dolado, A. and Kolb, H. and Triana-Baltzer, G. and Barthélemy, N. R. and Schindler, S. E. and Aschenbrenner, A. J. and Raji, C. A. and others},
title = {{A comprehensive head-to-head comparison of key plasma phosphorylated tau 217 biomarker tests}},
journal = {Brain},
year = {2025},
doi = {10.1093/brain/awae346},
pmid = {39468767},
url = {https://doi.org/10.1093/brain/awae346}
}
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Key findings
- Plasma %p-tau217WashU had the highest performance, with significantly higher AUCs than all the immunoassays (Pdiff < 0.007).
- Plasma %p-tau217WashU exhibited stronger associations with all PET load outcomes compared with immunoassays; baseline Aβ-PET load (R2: 0.72; immunoassays: 0.47-0.58; Pdiff < 0.001), baseline tau-PET load (R2: 0.51; immunoassays: 0.38-0.45; Pdiff < 0.001), longitudinal Aβ-PET load (R2: 0.53; immunoassays: 0.31-0.38; Pdiff < 0.001) and longitudinal tau-PET load (R2: 0.50; immunoassays: 0.35-0.43; Pdiff < 0.014).
- Among immunoassays, plasma p-tau217Lilly was more associated with Aβ-PET load than plasma p-tau217Janssen (Pdiff < 0.020) and with tau-PET load than both plasma p-tau217Janssen and plasma p-tau217ALZpath (all Pdiff < 0.010).
- The main results were replicated in an external cohort from Washington University in St Louis (n = 219).
- In summary, both mass spectrometry- and immunoassay-based p-tau217 tests generally perform well in identifying Aβ-PET, tau-PET and cognitive abnormalities, but %p-tau217WashU performed significantly better than all the examined immunoassays.
Why it matters
In a head-to-head comparison, the mass spectrometry-based %p-tau217WashU test performed significantly better than all immunoassays at identifying amyloid-PET, tau-PET, and cognitive abnormalities. The authors suggest %p-tau217 could serve as a stand-alone confirmatory test, while some immunoassays may be better suited as triage tests needing a second confirmation.
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Study details
- Study designcohort
- Participants998
- Effect sizeAccuracy for amyloid PET status 0.93 (%p-tau217 mass spectrometry) vs 0.83-0.88 (immunoassays)
- Evidence strengthHigh
Limitations
Amyloid PET was not available in patients with dementia by design; the longitudinal sample was smaller (n = 448); the authors call for replication in other cohorts because performance may depend on amyloid prevalence, demographics and kidney function (which affected non-ratio p-tau217 measures).
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 (Brain) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (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 | 2 / 4 | 998 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 | 5 / 7 | Cited 136 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 45.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 5 / 6 | Cited 37.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 17 other studies in this library |
| Still being cited | 3 / 4 | Cited 136 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 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 15 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39468767) |
| 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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