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Proteogenomics in cerebrospinal fluid and plasma reveals new biological fingerprint of cerebral small vessel disease
Ilana Caro, Daniel Western, Shinichi Namba, Na Sun, Shuji Kawaguchi, Yunye He, Masashi Fujita, Gennady V. Roshchupkin et al.. Nature Aging, 2025-11-20
Topic: Brain proteins, microglia and lab models
Cerebral small vessel disease (cSVD) is a leading cause of stroke and dementia with no specific treatment, of which molecular mechanisms remain poorly understood. To identify potential biomarkers and therapeutic targets, we applied Mendelian randomization to examine over 2,500 proteins measured in plasma and, uniquely, cerebrospinal fluid, in relation to magnetic resonance imaging (MRI) markers of cSVD in more than 40,000 individuals. Here we show that 49 proteins are associated with MRI markers of cSVD, most prominently in cerebrospinal fluid. We highlight associations that are consistent across platforms and ancestries, and supported by complementary observational analyses, and we explore differences between fluids. The proteins are enriched in pathways related to the extracellular matrix, immune response and microglial activity. Many also associate with stroke and dementia, and several correspond to existing drug targets. Together, these findings reveal a robust biological fingerprint of cSVD and highlight opportunities for biomarker and drug discovery and repositioning.
Key findings
- Here we show that 49 proteins are associated with MRI markers of cSVD, most prominently in cerebrospinal fluid.
- Together, these findings reveal a robust biological fingerprint of cSVD and highlight opportunities for biomarker and drug discovery and repositioning.
Why it matters
This study identified 49 proteins linked to MRI markers of small vessel disease, most prominently in cerebrospinal fluid, and many also linked to stroke and dementia. These findings point to possible biomarkers and drug targets, but no treatment was tested.
Study details
- Participants40,000
- Evidence strengthLow
How this study scored 52/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| 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 | 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 | 4 / 4 | 40,000 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 | 2 / 7 | Cited 6 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 3.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 6 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Stéphanie Debette: h-index 96 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 40 institution(s) in 9 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41266628) |
| Free to read | 2 / 2 | Free to read |
| Total | 52 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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
Caro, I., Western, D., Namba, S., Sun, N., Kawaguchi, S., He, Y., et al. (2025). Proteogenomics in cerebrospinal fluid and plasma reveals new biological fingerprint of cerebral small vessel disease. Nature Aging. https://doi.org/10.1038/s43587-025-01006-w
Vancouver
Caro I, Western D, Namba S, Sun N, Kawaguchi S, He Y, et al. Proteogenomics in cerebrospinal fluid and plasma reveals new biological fingerprint of cerebral small vessel disease. Nature Aging. 2025. doi:10.1038/s43587-025-01006-w. PMID: 41266628.
BibTeX
@article{caro2025-41266628,
author = {Caro, Ilana and Western, Daniel and Namba, Shinichi and Sun, Na and Kawaguchi, Shuji and He, Yunye and Fujita, Masashi and Roshchupkin, Gennady V. and others},
title = {{Proteogenomics in cerebrospinal fluid and plasma reveals new biological fingerprint of cerebral small vessel disease}},
journal = {Nature Aging},
year = {2025},
doi = {10.1038/s43587-025-01006-w},
pmid = {41266628},
url = {https://doi.org/10.1038/s43587-025-01006-w}
}
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