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A two-step workflow based on plasma p-tau217 to screen for amyloid β positivity with further confirmatory testing only in uncertain cases
Brum WS, Cullen NC, Janelidze S, Ashton NJ, Zimmer ER, Therriault J, Benedet AL, Rahmouni N, Tissot C, Stevenson J, Servaes S, Triana-Baltzer G, et al.. Nature Aging, 2023-08-31
Topic: Amyloid, tau and blood-test diagnosis
Cost-effective strategies for identifying amyloid-β (Aβ) positivity in patients with cognitive impairment are urgently needed with recent approvals of anti-Aβ immunotherapies for Alzheimer's disease (AD). Blood biomarkers can accurately detect AD pathology, but it is unclear whether their incorporation into a full diagnostic workflow can reduce the number of confirmatory cerebrospinal fluid (CSF) or positron emission tomography (PET) tests needed while accurately classifying patients. We evaluated a two-step workflow for determining Aβ-PET status in patients with mild cognitive impairment (MCI) from two independent memory clinic-based cohorts (n = 348). A blood-based model including plasma tau protein 217 (p-tau217), age and APOE ε4 status was developed in BioFINDER-1 (area under the curve (AUC) = 89.3%) and validated in BioFINDER-2 (AUC = 94.3%). In step 1, the blood-based model was used to stratify the patients into low, intermediate or high risk of Aβ-PET positivity. In step 2, we assumed referral only of intermediate-risk patients to CSF Aβ42/Aβ40 testing, whereas step 1 alone determined Aβ-status for low- and high-risk groups. Depending on whether lenient, moderate or stringent thresholds were used in step 1, the two-step workflow overall accuracy for detecting Aβ-PET status was 88.2%, 90.5% and 92.0%, respectively, while reducing the number of necessary CSF tests by 85.9%, 72.7% and 61.2%, respectively. In secondary analyses, an adapted version of the BioFINDER-1 model led to successful validation of the two-step workflow with a different plasma p-tau217 immunoassay in patients with cognitive impairment from the TRIAD cohort (n = 84). In conclusion, using a plasma p-tau217-based model for risk stratification of patients with MCI can substantially reduce the need for confirmatory testing while accurately classifying patients, offering a cost-effective strategy to detect AD in memory clinic settings.
Key findings
- Depending on whether lenient, moderate or stringent thresholds were used in step 1, the two-step workflow overall accuracy for detecting Aβ-PET status was 88.2%, 90.5% and 92.0%, respectively, while reducing the number of necessary CSF tests by 85.9%, 72.7% and 61.2%, respectively.
- In conclusion, using a plasma p-tau217-based model for risk stratification of patients with MCI can substantially reduce the need for confirmatory testing while accurately classifying patients, offering a cost-effective strategy to detect AD in memory clinic settings.
Why it matters
A two-step workflow using a plasma p-tau217-based model to stratify patients with mild cognitive impairment achieved 88.2% to 92.0% accuracy for detecting amyloid-PET status while reducing needed cerebrospinal fluid tests by 61.2% to 85.9%. This could make diagnostic testing more cost-effective, though it was evaluated in memory clinic cohorts.
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Study details
- Study designcohort
- Participants348
- Effect sizeAccuracy 88-92% with 61-86% fewer CSF tests
- Evidence strengthHigh
Limitations
Plasma biomarkers were measured in single batches, as is standard in cohort studies, so assays, cut-offs and model strategies must be prospectively validated before routine use; further validation in diverse populations and settings is warranted.
How this study scored 77/100
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 75 of the 98 points we could judge it on, which is 77 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature Aging) |
| Journal's citation record | 1 / 4 | Nature Aging: journal h-index 103 (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 | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 348 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 245 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 49.0 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 6 / 6 | Cited 44.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 33 other studies in this library |
| Still being cited | 4 / 4 | Cited 237 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 | McGill University: institution h-index 1,373 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 11 institution(s) in 6 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37653254) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 75 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 75 of the 98 points we could judge it on is 77 out of 100. |
| Total | 77 / 100 | — |
What each of these 20 components measures, and what this score is not →
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
Brum, W. S., Cullen, N. C., Janelidze, S., Ashton, N. J., Zimmer, E. R., Therriault, J., et al. (2023). A two-step workflow based on plasma p-tau217 to screen for amyloid β positivity with further confirmatory testing only in uncertain cases. Nature Aging. https://doi.org/10.1038/s43587-023-00471-5
Vancouver
Brum WS, Cullen NC, Janelidze S, Ashton NJ, Zimmer ER, Therriault J, et al. A two-step workflow based on plasma p-tau217 to screen for amyloid β positivity with further confirmatory testing only in uncertain cases. Nature Aging. 2023. doi:10.1038/s43587-023-00471-5. PMID: 37653254.
BibTeX
@article{brum2023-37653254,
author = {Brum, W. S. and Cullen, N. C. and Janelidze, S. and Ashton, N. J. and Zimmer, E. R. and Therriault, J. and Benedet, A. L. and Rahmouni, N. and Tissot, C. and Stevenson, J. and Servaes, S. and Triana-Baltzer, G. and others},
title = {{A two-step workflow based on plasma p-tau217 to screen for amyloid β positivity with further confirmatory testing only in uncertain cases}},
journal = {Nature Aging},
year = {2023},
doi = {10.1038/s43587-023-00471-5},
pmid = {37653254},
url = {https://doi.org/10.1038/s43587-023-00471-5}
}
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