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Large-scale CSF proteome profiling identifies biomarkers for accurate diagnosis of frontotemporal dementia
Yanaika Sylvana Hok-A-Hin, Lisa Vermunt, Carel F.W. Peeters, Emma Louise van der Ende, Sterre C.M. de Boer, Lieke H. H. Meeter, Julie F. H. De Houwer, Harro Seelaar et al.. Molecular Neurodegeneration, 2025-08-27
Topic: Brain proteins, microglia and lab models
Forty-three proteins were differentially regulated in FTD compared to controls and AD, reflecting axon development, regulation of synapse assembly, and cell-cell adhesion mediator activity pathways. Classification analysis identified a 14- and 13-CSF protein panel that discriminated FTD from controls (FTD diagnostic panel, AUC: 0.96) or AD (FTD differential diagnostic panel, AUC: 0.91). Custom multiplex panels confirmed the strong discriminative performancen between FTD and controls (AUCs > 0.96) and between FTD and AD (AUCs > 0.88) across three validation cohorts, including one with autopsy confirmation (AUCs > 0.90). Validation in genetic FTD (including C9orf72, GRN, and MAPT mutation carriers) revealed high accuracy of the FTD diagnostic panel in identifying both the presymptomatic (AUCs > 0.95) and symptomatic (AUC: 1) stages. Six proteins were differentially regulated between FTLD-TDP and FTLD-Tau. However, a reproducible classification model could not be generated (AUC: 0.80). Overall, this study introduces novel FTD-specific biomarker panels with potential use in diagnostic settings.
Key findings
- Forty-three proteins were differentially regulated in FTD compared to controls and AD, reflecting axon development, regulation of synapse assembly, and cell-cell adhesion mediator activity pathways.
- Classification analysis identified a 14- and 13-CSF protein panel that discriminated FTD from controls (FTD diagnostic panel, AUC: 0.96) or AD (FTD differential diagnostic panel, AUC: 0.91).
- Custom multiplex panels confirmed the strong discriminative performancen between FTD and controls (AUCs > 0.96) and between FTD and AD (AUCs > 0.88) across three validation cohorts, including one with autopsy confirmation (AUCs > 0.90).
- Validation in genetic FTD (including C9orf72, GRN, and MAPT mutation carriers) revealed high accuracy of the FTD diagnostic panel in identifying both the presymptomatic (AUCs > 0.95) and symptomatic (AUC: 1) stages.
- Six proteins were differentially regulated between FTLD-TDP and FTLD-Tau.
Why it matters
This study identified cerebrospinal fluid protein panels that accurately discriminate frontotemporal dementia from controls and Alzheimer's disease. It introduces potential diagnostic biomarkers, but it does not report any treatment, cure, or prevention for Alzheimer's disease.
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Study details
- Participants189
- Effect sizeAUC: 0.96; AUC: 0.91; AUC: 0.80
- Evidence strengthModerate
How this study scored 55/100
Published in a peer-reviewed journal. Scored zero for study design and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular Neurodegeneration) |
| Journal's citation record | 2 / 4 | Molecular Neurodegeneration: journal h-index 164 (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 | 3 / 5 | Rated “moderate” 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 | 189 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | 2 / 7 | Cited 9 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 5.7× 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 | 1 / 4 | Cited 9 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Marta del Campo: h-index 24 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Pennsylvania: institution h-index 1,859 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 18 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40866991) |
| Free to read | 2 / 2 | Free to read |
| Total | 55 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s13024-025-00882-5
- PubMed: 40866991
- Original source →
- Free full text: Molecular Neurodegeneration →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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
Hok-A-Hin, Y. S., Vermunt, L., Peeters, C. F., van der Ende, E. L., de Boer, S. C., Meeter, L. H. H., et al. (2025). Large-scale CSF proteome profiling identifies biomarkers for accurate diagnosis of frontotemporal dementia. Molecular Neurodegeneration. https://doi.org/10.1186/s13024-025-00882-5
Vancouver
Hok-A-Hin YS, Vermunt L, Peeters CF, van der Ende EL, de Boer SC, Meeter LHH, et al. Large-scale CSF proteome profiling identifies biomarkers for accurate diagnosis of frontotemporal dementia. Molecular Neurodegeneration. 2025. doi:10.1186/s13024-025-00882-5. PMID: 40866991.
BibTeX
@article{hokahin2025-40866991,
author = {Hok-A-Hin, Yanaika Sylvana and Vermunt, Lisa and Peeters, Carel F.W. and van der Ende, Emma Louise and de Boer, Sterre C.M. and Meeter, Lieke H. H. and De Houwer, Julie F. H. and Seelaar, Harro and others},
title = {{Large-scale CSF proteome profiling identifies biomarkers for accurate diagnosis of frontotemporal dementia}},
journal = {Molecular Neurodegeneration},
year = {2025},
doi = {10.1186/s13024-025-00882-5},
pmid = {40866991},
url = {https://doi.org/10.1186/s13024-025-00882-5}
}
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