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Does CSF testing add value after an indeterminate plasma p-tau217 result?
Bernardi E, Arranz J, Rubio-Guerra S, García-Castro J, Maure-Blesa L, Rodríguez-Baz I, Peris-Subiza J, Selma-González J et al.. Research Square, 2026-09-01
Topic: Plasma and spinal-fluid biomarkers
Background It is unclear whether cerebrospinal fluid (CSF) testing improves classification when plasma phosphorylated tau 217 (p-tau217) results are indeterminate. Using amyloid and tau positron emission tomography (PET) as the reference standard, we compared plasma p-tau217 with core CSF biomarkers and evaluated a sequential plasma-to-CSF workflow. Methods We studied 283 Alzheimer's Disease Neuroimaging Initiative participants (148 cognitively unimpaired [CU]; 135 symptomatic) with concurrent plasma p-tau217, CSF biomarkers and amyloid PET; 265 also had tau PET. Amyloid positivity was defined at 18, 37 and 45 Centiloids (CL). Areas under the receiver operating characteristic curve (AUC) were compared with paired DeLong tests and false discovery rate (FDR) correction. Indeterminate plasma results (between the 95%-sensitivity and 95%-specificity thresholds) were resolved with internally optimized CSF p-tau181/Aβ42 or Aβ42/40 cutoffs; incremental value was assessed with net reclassification improvement (NRI) and McNemar tests. Results Mean (SD) age was 71 (7) years; 153 (54%) were women. No AUC difference between plasma p-tau217 and either CSF biomarker survived FDR correction, in either group, at any CL threshold or Braak stage. Internally optimal plasma p-tau217 thresholds shifted with clinical status and with the target amyloid and tau burden. Sequential CSF testing did not significantly improve classification (amyloid NRI 0.01 to 0.10; tau NRI − 0.09 to 0.08) and misclassified up to 27% (amyloid) and 33% (tau) of indeterminate cases. Conclusions These data are compatible with, but do not establish, equivalence between plasma p-tau217 and CSF biomarkers. When plasma results were indeterminate, CSF testing did not reduce uncertainty in this cohort. Clinical trial number: not applicable.
Key findings
- Background It is unclear whether cerebrospinal fluid (CSF) testing improves classification when plasma phosphorylated tau 217 (p-tau217) results are indeterminate.
- Areas under the receiver operating characteristic curve (AUC) were compared with paired DeLong tests and false discovery rate (FDR) correction.
- Indeterminate plasma results (between the 95%-sensitivity and 95%-specificity thresholds) were resolved with internally optimized CSF p-tau181/Aβ42 or Aβ42/40 cutoffs; incremental value was assessed with net reclassification improvement (NRI) and McNemar tests.
- Results Mean (SD) age was 71 (7) years; 153 (54%) were women.
- Sequential CSF testing did not significantly improve classification (amyloid NRI 0.01 to 0.10; tau NRI − 0.09 to 0.08) and misclassified up to 27% (amyloid) and 33% (tau) of indeterminate cases.
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Study details
- Participants283
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 35 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 22 of the 62 points we could judge it on, which is 35 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 283 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 22 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 22 of the 62 points we could judge it on is 35 out of 100. |
| Total | 35 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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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
Bernardi, E., Arranz, J., Rubio-Guerra, S., García-Castro, J., Maure-Blesa, L., Rodríguez-Baz, I., et al. (2026). Does CSF testing add value after an indeterminate plasma p-tau217 result? Research Square. https://doi.org/10.21203/rs.3.rs-10754560/v1
Vancouver
Bernardi E, Arranz J, Rubio-Guerra S, García-Castro J, Maure-Blesa L, Rodríguez-Baz I, et al. Does CSF testing add value after an indeterminate plasma p-tau217 result? Research Square. 2026. doi:10.21203/rs.3.rs-10754560/v1.
BibTeX
@article{bernardi2026-632475b0,
author = {Bernardi, E. and Arranz, J. and Rubio-Guerra, S. and García-Castro, J. and Maure-Blesa, L. and Rodríguez-Baz, I. and Peris-Subiza, J. and Selma-González, J. and others},
title = {{Does CSF testing add value after an indeterminate plasma p-tau217 result?}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-10754560/v1},
url = {https://doi.org/10.21203/rs.3.rs-10754560/v1}
}
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