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Plasma vesicle-associated membrane protein 2 and glial fibrillary acidic protein associate with synaptic density in older adults without dementia
Steffi De Meyer, Soha Alali, Maarten Laroy, Thomas Vande Casteele, Margot Van Cauwenberge, Julie Goossens, Charlotte De Rocker, Jeroen Vanbrabant et al.. Brain Communications, 2025-01-01
Topic: Brain proteins, microglia and lab models
The study population demonstrated limited PET-based amyloid-β and tau pathology, which did not associate with any of the investigated plasma biomarkers. Plasma vesicle-associated membrane protein 2 associated with synaptic vesicle glycoprotein 2A PET within frontal, temporal, and occipital cortices [βs (95% confidence interval) −0.75 (−1.06 to −0.44)], independent of age. Glial fibrillary acidic protein also demonstrated associations with synaptic vesicle glycoprotein 2A PET, particularly within temporal regions, the cingulate gyrus, and the precuneus [βs (95% confidence interval) −0.30 (−0.48 to −0.12)] when corrected for age and additionally within the caudate nucleus and thalamus when not [βs (95% confidence interval) −0.45 (−0.64 to −0.25)]. GM volume associated with glial fibrillary acidic protein [βs (95% confidence interval) −0.15 (−0.25 to −0.05)] and partially (29%) mediated its association with synaptic vesicle glycoprotein 2A PET. In conclusion, plasma levels of glial fibrillary acidic protein and vesicle-associated membrane protein 2 may reflect synapse pathology independent of age and beyond general neuronal loss, even in absence of detectable Alzheimer’s disease pathology.
Key findings
- The study population demonstrated limited PET-based amyloid-β and tau pathology, which did not associate with any of the investigated plasma biomarkers.
- Plasma vesicle-associated membrane protein 2 associated with synaptic vesicle glycoprotein 2A PET within frontal, temporal, and occipital cortices [βs (95% confidence interval) −0.75 (−1.06 to −0.44)], independent of age.
- Glial fibrillary acidic protein also demonstrated associations with synaptic vesicle glycoprotein 2A PET, particularly within temporal regions, the cingulate gyrus, and the precuneus [βs (95% confidence interval) −0.30 (−0.48 to −0.12)] when corrected for age and additionally within the caudate nucleus and thalamus when not [βs (95% confidence interval) −0.45 (−0.64 to −0.25)].
- GM volume associated with glial fibrillary acidic protein [βs (95% confidence interval) −0.15 (−0.25 to −0.05)] and partially (29%) mediated its association with synaptic vesicle glycoprotein 2A PET.
- In conclusion, plasma levels of glial fibrillary acidic protein and vesicle-associated membrane protein 2 may reflect synapse pathology independent of age and beyond general neuronal loss, even in absence of detectable Alzheimer’s disease pathology.
Why it matters
In older adults without dementia who had limited amyloid-β and tau pathology on PET, plasma VAMP2 and GFAP were associated with synaptic vesicle glycoprotein 2A PET, suggesting they may reflect synapse pathology. This is a cross-sectional biomarker study and does not test any treatment, cure or prevention.
Study details
- Study designcross-sectional
- Participants49
- Evidence strengthLow
How this study scored 45/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain Communications) |
| Journal's citation record | 0 / 4 | Brain Communications: journal h-index 67 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| 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 | 49 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 | 1 / 7 | Cited 3 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.9× 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 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Koen Poesen: h-index 38 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | KU Leuven: institution h-index 1,386 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40620474) |
| Free to read | 2 / 2 | Free to read |
| Total | 45 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1093/braincomms/fcaf207
- PubMed: 40620474
- Original source →
- Free full text: Brain Communications →
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
De Meyer, S., Alali, S., Laroy, M., Casteele, T. V., Van Cauwenberge, M., Goossens, J., et al. (2025). Plasma vesicle-associated membrane protein 2 and glial fibrillary acidic protein associate with synaptic density in older adults without dementia. Brain Communications. https://doi.org/10.1093/braincomms/fcaf207
Vancouver
De Meyer S, Alali S, Laroy M, Casteele TV, Van Cauwenberge M, Goossens J, et al. Plasma vesicle-associated membrane protein 2 and glial fibrillary acidic protein associate with synaptic density in older adults without dementia. Brain Communications. 2025. doi:10.1093/braincomms/fcaf207. PMID: 40620474.
BibTeX
@article{demeyer2025-40620474,
author = {De Meyer, Steffi and Alali, Soha and Laroy, Maarten and Casteele, Thomas Vande and Van Cauwenberge, Margot and Goossens, Julie and De Rocker, Charlotte and Vanbrabant, Jeroen and others},
title = {{Plasma vesicle-associated membrane protein 2 and glial fibrillary acidic protein associate with synaptic density in older adults without dementia}},
journal = {Brain Communications},
year = {2025},
doi = {10.1093/braincomms/fcaf207},
pmid = {40620474},
url = {https://doi.org/10.1093/braincomms/fcaf207}
}
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