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Comparing the Clinical Utility and Diagnostic Performance of CSF P-Tau181, P-Tau217, and P-Tau231 Assays
Leuzy A, Janelidze S, Mattsson-Carlgren N, Palmqvist S, Jacobs D, Cicognola C, Stomrud E, Vanmechelen E et al.. Neurology, 2021-09-07
Topic: Brain proteins, microglia and lab models
Background and objectives Phosphorylated tau (p-tau) in CSF is considered an important biomarker in Alzheimer disease (AD) and has been incorporated in recent diagnostic criteria. Several variants exist, including p-tau at threonines 181 (p-tau181), 217 (p-tau217), and 231 (p-tau231). However, no studies have compared their diagnostic performance or association to β-amyloid (Aβ) and tau-PET. Understanding which p-tau variant to use remains an important yet answered question. We aimed to compare the diagnostic accuracy of p-tau181, p-tau217, and p-tau231 in CSF for AD and their association with Aβ and tau-PET. Methods A total of 629 participants in the Swedish BioFINDER-2 study were included (cognitively unimpaired, n = 334; Aβ-positive mild cognitive impairment, n = 84; AD dementia, n = 119; and non-AD disorders, n = 92). In addition to p-tau181 and p-tau217 measured using assays with the same detector antibodies from Eli Lilly (p-tau181 Lilly , p-tau217 Lilly ) and p-tau231, we also included p-tau181 measurements from 2 commonly used assays (Innotest and Elecsys). Results Although all p-tau variants increased across the AD continuum, p-tau217 Lilly showed the greatest dynamic range (13-fold increase vs 1.9-5.4-fold increase for other p-tau variants for AD dementia vs non-AD). P-Tau217 Lilly showed stronger correlations with Aβ- and tau-PET ( p Lilly exhibited higher accuracy than other p-tau variants for separating AD dementia from non-AD (area under the curve [AUC], 0.98 vs 0.88 [ p p p p p Lilly generally performed better than the other p-tau181 assays (e.g., AD dementia vs non-AD, AUC, 0.96 vs 0.88 [p-tau181 Innotest ] and 0.89 [p-tau181 Elecsys ]; p Discussion CSF p-tau217 Lilly seems to be more useful than other included p-tau assays in the workup of AD. Varied results across p-tau181 assays highlights the importance of anti-tau antibodies for biomarker performance. Classification of evidence This study provides Class II evidence that p-tau217 provides higher diagnostic accuracy for diagnosis of AD dementia than p-tau181 or p-tau231.
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APA 7th
Leuzy, A., Janelidze, S., Mattsson-Carlgren, N., Palmqvist, S., Jacobs, D., Cicognola, C., et al. (2021). Comparing the Clinical Utility and Diagnostic Performance of CSF P-Tau181, P-Tau217, and P-Tau231 Assays. Neurology. https://doi.org/10.1212/wnl.0000000000012727
Vancouver
Leuzy A, Janelidze S, Mattsson-Carlgren N, Palmqvist S, Jacobs D, Cicognola C, et al. Comparing the Clinical Utility and Diagnostic Performance of CSF P-Tau181, P-Tau217, and P-Tau231 Assays. Neurology. 2021. doi:10.1212/wnl.0000000000012727. PMID: 34493616.
BibTeX
@article{leuzy2021-34493616,
author = {Leuzy, A. and Janelidze, S. and Mattsson-Carlgren, N. and Palmqvist, S. and Jacobs, D. and Cicognola, C. and Stomrud, E. and Vanmechelen, E. and others},
title = {{Comparing the Clinical Utility and Diagnostic Performance of CSF P-Tau181, P-Tau217, and P-Tau231 Assays}},
journal = {Neurology},
year = {2021},
doi = {10.1212/wnl.0000000000012727},
pmid = {34493616},
url = {https://doi.org/10.1212/wnl.0000000000012727}
}
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
- Results Although all p-tau variants increased across the AD continuum, p-tau217 Lilly showed the greatest dynamic range (13-fold increase vs 1.9-5.4-fold increase for other p-tau variants for AD dementia vs non-AD).
- Varied results across p-tau181 assays highlights the importance of anti-tau antibodies for biomarker performance.
Why it matters
Comparing CSF p-tau variants, p-tau217 showed the largest increase across the Alzheimer's continuum and stronger links to amyloid and tau PET than the other variants. This is a biomarker comparison for diagnosis and does not test any treatment, cure, or prevention.
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Study details
- Participants334
- Evidence strengthLow
How this study scored 61/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 334 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| 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 127 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 18.1 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 4 / 6 | Cited 13.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 19 other studies in this library |
| Still being cited | 3 / 4 | Cited 73 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 | 1 / 3 | Lund University: institution h-index 1,119 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34493616) |
| Free to read | 2 / 2 | Free to read |
| Total | 61 / 100 | — |
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Read the original
- DOI: 10.1212/wnl.0000000000012727
- PubMed: 34493616
- 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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