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Dissection of blood-brain barrier dysfunction through CSF PDGFRβ and amyloid, tau, neuroinflammation, and synaptic CSF biomarkers in neurodegenerative disorders
Vrillon A, Ashton NJ, Bouaziz-Amar E, Mouton-Liger F, Cognat E, Dumurgier J, Lilamand M, Karikari TK et al.. EBioMedicine, 2025-04-15
Topic: Brain proteins, microglia and lab models
Background Blood-brain barrier (BBB) dysfunction is an early event in neurodegenerative disorders. Pericytes are key cells for BBB maintenance. Upon pericyte injury, the platelet-derived growth factor receptor-β (PDGFRβ) is released in the cerebrospinal fluid (CSF). The relation of CSF PDGFRβ with markers of amyloid pathology, neuroinflammation, and axonal and synaptic damage across dementia remains unclear. Methods Retrospectively, we quantified CSF PDGFRβ and CSF core Alzheimer's disease (AD), astrocytic (GFAP), microglial (sTREM 2, YKL-40), axonal (NfL), and synaptic (GAP-43, neurogranin) biomarkers in 210 patients from the Cognitive Neurology Centre, Paris, France, including n = 23 neurological controls (NC), n = 84 patients with mild cognitive impairment (MCI) [AD, n = 41; non-AD, n = 43], and n = 103 patients with dementia (AD, n = 73; non-AD, n = 30). Findings Comparing clinical stages, CSF PDGFRβ levels were increased at the MCI stage (Cohen's d = 0.55 [CI 95% 0.066, 1.0], P = 0.025) compared with NC. Non-AD MCI displayed higher levels than controls (Cohen's d = 0.74 [CI 95% 0.22, 1.3], P = 0.042). No association was observed with CSF Aβ42/Aβ40 ratio but with p-tau 181 (β = 0.102 [CI 95% 0.027, 0.176], P = 0.0080) and t-tau levels (β = 0.133 [0.054, 0.213], P = 0.0010). CSF PDGFRβ levels were positively associated with CSF neuroinflammation and synaptic markers levels. Higher CSF PDGFRβ levels were associated with lower MMSE scores at MCI (β = -1.23 [CI 95% -2.33, -0.260], P = 0.015) and dementia stages (β = -2.24 [CI 95% -3.62, -0.85], P = 0.0020). CSF neuroinflammation biomarkers mediated the association of CSF PDGFRβ with neurodegeneration and synaptic integrity markers. Interpretation CSF PDGFRβ, a candidate biomarker of BBB dysfunction, is increased in the early stages of neurodegenerative disorders, in association with neuroinflammation and axonal and synaptic damage. Funding Association des Anciens Internes des Hôpitaux de Paris, Edmond de Rothschild Program, Fondation Vaincre Alzheimer, Demensförbundet, Gamla Tjänarinnor, Anna-Lisa och Bror Björnssons Stiftelse.
Key findings
- Findings Comparing clinical stages, CSF PDGFRβ levels were increased at the MCI stage (Cohen's d = 0.55 [CI 95% 0.066, 1.0], P = 0.025) compared with NC.
- CSF PDGFRβ levels were positively associated with CSF neuroinflammation and synaptic markers levels.
- Higher CSF PDGFRβ levels were associated with lower MMSE scores at MCI (β = -1.23 [CI 95% -2.33, -0.260], P = 0.015) and dementia stages (β = -2.24 [CI 95% -3.62, -0.85], P = 0.0020).
Why it matters
In this study of 210 patients, a marker of pericyte injury called CSF PDGFRβ was higher at the mild cognitive impairment stage and was linked to markers of neuroinflammation, synaptic damage and worse cognitive scores. This is an observational study and does not show that targeting this marker changes the course of disease.
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Study details
- Participants23
- Evidence strengthLow
How this study scored 51/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (EBioMedicine) |
| Journal's citation record | 2 / 4 | EBioMedicine: journal h-index 181 (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 | 1 / 4 | 23 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 | 3 / 7 | Cited 25 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 7.6× 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 | 2 / 4 | Cited 25 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Claire Paquet: h-index 56 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 25 institution(s) in 6 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40239464) |
| Free to read | 2 / 2 | Free to read |
| Total | 51 / 100 | — |
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Read the original
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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
Vrillon, A., Ashton, N. J., Bouaziz-Amar, E., Mouton-Liger, F., Cognat, E., Dumurgier, J., et al. (2025). Dissection of blood-brain barrier dysfunction through CSF PDGFRβ and amyloid, tau, neuroinflammation, and synaptic CSF biomarkers in neurodegenerative disorders. EBioMedicine. https://doi.org/10.1016/j.ebiom.2025.105694
Vancouver
Vrillon A, Ashton NJ, Bouaziz-Amar E, Mouton-Liger F, Cognat E, Dumurgier J, et al. Dissection of blood-brain barrier dysfunction through CSF PDGFRβ and amyloid, tau, neuroinflammation, and synaptic CSF biomarkers in neurodegenerative disorders. EBioMedicine. 2025. doi:10.1016/j.ebiom.2025.105694. PMID: 40239464.
BibTeX
@article{vrillon2025-40239464,
author = {Vrillon, A. and Ashton, N. J. and Bouaziz-Amar, E. and Mouton-Liger, F. and Cognat, E. and Dumurgier, J. and Lilamand, M. and Karikari, T. K. and others},
title = {{Dissection of blood-brain barrier dysfunction through CSF PDGFRβ and amyloid, tau, neuroinflammation, and synaptic CSF biomarkers in neurodegenerative disorders}},
journal = {EBioMedicine},
year = {2025},
doi = {10.1016/j.ebiom.2025.105694},
pmid = {40239464},
url = {https://doi.org/10.1016/j.ebiom.2025.105694}
}
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