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Cerebrospinal fluid proteomics identification of biomarkers for amyloid and tau PET stages
Zhibo Wang, Yuhan Chen, Katherine Gong, Bote Zhao, Yuye Ning, Meilin Chen, Yan Li, Muhammad Ali et al.. Cell reports. Medicine, 2025-03-20
Topic: Plasma and spinal-fluid biomarkers
Accurate staging of Alzheimer's disease (AD) pathology is crucial for therapeutic trials and prognosis, but existing fluid biomarkers lack specificity, especially for assessing tau deposition severity, in amyloid-beta (Aβ)-positive patients. We analyze cerebrospinal fluid (CSF) samples from 136 participants in the Alzheimer's Disease Neuroimaging Initiative using more than 6,000 proteins. We apply machine learning to predict AD pathological stages defined by amyloid and tau positron emission tomography (PET). We identify two distinct protein panels: 16 proteins, including neurofilament heavy chain (NEFH) and SPARC-related modular calcium-binding protein 1 (SMOC1), that distinguished Aβ-negative/tau-negative (A-T-) from A+ individuals and nine proteins, such as HCLS1-associated protein X-1 (HAX1) and glucose-6-phosphate isomerase (GPI), that differentiated A+T+ from A+T- stages. These signatures outperform the established CSF biomarkers (area under the curve [AUC]: 0.92 versus 0.67-0.70) and accurately predicted disease progression over a decade. The findings are validated in both internal and external cohorts. These results underscore the potential of proteomic-based signatures to refine AD diagnostic criteria and improve patient stratification in clinical trials.
Key findings
- These signatures outperform the established CSF biomarkers (area under the curve [AUC]: 0.92 versus 0.67-0.70) and accurately predicted disease progression over a decade.
- These results underscore the potential of proteomic-based signatures to refine AD diagnostic criteria and improve patient stratification in clinical trials.
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Study details
- Participants136
- Evidence strengthLow
How this study scored 52/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, 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, multi-centre collaboration and free to read, so those were left out: it earned 29 of the 56 points we could judge it on, which is 52 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cell reports. Medicine) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 136 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 | 2 / 2 | Indexed in PubMed (PMID 40118053) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 29 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 29 of the 56 points we could judge it on is 52 out of 100. |
| Total | 52 / 100 | — |
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APA 7th
Wang, Z., Chen, Y., Gong, K., Zhao, B., Ning, Y., Chen, M., et al. (2025). Cerebrospinal fluid proteomics identification of biomarkers for amyloid and tau PET stages. Cell reports. Medicine. https://doi.org/10.1016/j.xcrm.2025.102031
Vancouver
Wang Z, Chen Y, Gong K, Zhao B, Ning Y, Chen M, et al. Cerebrospinal fluid proteomics identification of biomarkers for amyloid and tau PET stages. Cell reports. Medicine. 2025. doi:10.1016/j.xcrm.2025.102031. PMID: 40118053.
BibTeX
@article{wang2025-40118053,
author = {Wang, Zhibo and Chen, Yuhan and Gong, Katherine and Zhao, Bote and Ning, Yuye and Chen, Meilin and Li, Yan and Ali, Muhammad and others},
title = {{Cerebrospinal fluid proteomics identification of biomarkers for amyloid and tau PET stages}},
journal = {Cell reports. Medicine},
year = {2025},
doi = {10.1016/j.xcrm.2025.102031},
pmid = {40118053},
url = {https://doi.org/10.1016/j.xcrm.2025.102031}
}