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A Pragmatic, Data-Driven Method to Determine Cutoffs for CSF Biomarkers of Alzheimer Disease Based on Validation Against PET Imaging
Dumurgier J, Sabia S, Zetterberg H, Teunissen CE, Hanseeuw B, Orellana A, Schraen S, Gabelle A et al.. Neurology, 2022-05-26
Topic: Amyloid, tau and blood-test diagnosis
Background and objectives To elaborate a new algorithm to establish a standardized method to define cutoffs for CSF biomarkers of Alzheimer disease (AD) by validating the algorithm against CSF classification derived from PET imaging. Methods Low and high levels of CSF phosphorylated tau were first identified to establish optimal cutoffs for CSF β-amyloid (Aβ) peptide biomarkers. These Aβ cutoffs were then used to determine cutoffs for CSF tau and phosphorylated tau markers. We compared this algorithm to a reference method, based on tau and amyloid PET imaging status (ADNI study), and then applied the algorithm to 10 large clinical cohorts of patients. Results A total of 6,922 patients with CSF biomarker data were included (mean [SD] age: 70.6 [8.5] years, 51.0% women). In the ADNI study population (n = 497), the agreement between classification based on our algorithm and the one based on amyloid/tau PET imaging was high, with Cohen's kappa coefficient between 0.87 and 0.99. Applying the algorithm to 10 large cohorts of patients (n = 6,425), the proportion of persons with AD ranged from 25.9% to 43.5%. Discussion The proposed novel, pragmatic method to determine CSF biomarker cutoffs for AD does not require assessment of other biomarkers or assumptions concerning the clinical diagnosis of patients. Use of this standardized algorithm is likely to reduce heterogeneity in AD classification.
Key findings
- Results A total of 6,922 patients with CSF biomarker data were included (mean [SD] age: 70.6 [8.5] years, 51.0% women).
Why it matters
A new method for setting cutoff values for Alzheimer's spinal fluid biomarkers agreed closely with amyloid and tau PET imaging in one study group and was then applied to 10 large patient groups. This is a way to standardize diagnosis, not a treatment, cure or prevention.
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Study details
- Participants497
- Effect size51.0%; 25.9% to 43.5%
- Evidence strengthLow
How this study scored 58/100
Published in a leading specialty journal. Scored zero for study design and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 56 of the 96 points we could judge it on, which is 58 out of 100.
| 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 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 497 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 | 3 / 7 | Cited 31 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.2 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 3 / 6 | Cited 3.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 2 / 4 | Cited 23 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 17 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35970577) |
| Free to read | 2 / 2 | Free to read |
| Points | 56 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 56 of the 96 points we could judge it on is 58 out of 100. |
| Total | 58 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1212/wnl.0000000000200735
- PubMed: 35970577
- 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).
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
Dumurgier, J., Sabia, S., Zetterberg, H., Teunissen, C. E., Hanseeuw, B., Orellana, A., et al. (2022). A Pragmatic, Data-Driven Method to Determine Cutoffs for CSF Biomarkers of Alzheimer Disease Based on Validation Against PET Imaging. Neurology. https://doi.org/10.1212/wnl.0000000000200735
Vancouver
Dumurgier J, Sabia S, Zetterberg H, Teunissen CE, Hanseeuw B, Orellana A, et al. A Pragmatic, Data-Driven Method to Determine Cutoffs for CSF Biomarkers of Alzheimer Disease Based on Validation Against PET Imaging. Neurology. 2022. doi:10.1212/wnl.0000000000200735. PMID: 35970577.
BibTeX
@article{dumurgier2022-35970577,
author = {Dumurgier, J. and Sabia, S. and Zetterberg, H. and Teunissen, C. E. and Hanseeuw, B. and Orellana, A. and Schraen, S. and Gabelle, A. and others},
title = {{A Pragmatic, Data-Driven Method to Determine Cutoffs for CSF Biomarkers of Alzheimer Disease Based on Validation Against PET Imaging}},
journal = {Neurology},
year = {2022},
doi = {10.1212/wnl.0000000000200735},
pmid = {35970577},
url = {https://doi.org/10.1212/wnl.0000000000200735}
}
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