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Synaptosomal‐Associated Protein 25 kDA (SNAP‐25) Levels in Cerebrospinal Fluid: Implications for Alzheimer's Disease Diagnosis and Monitoring
Sofia Hjorth Wolner, Helena Sophia Gleerup, Christian Sandøe Musaeus, Peter Høgh, Nicholas J. Ashton, Ann Brinkmalm, Johanna E. Nilsson, Lana Grötschel et al.. Synapse, 2025-02-06
Topic: Brain proteins, microglia and lab models
Synaptic degeneration has been linked to cognitive decline. The presynaptic protein, synaptosomal-associated protein 25 kDA (SNAP-25), is crucial for synaptic transmission and has been suggested as a biomarker in Alzheimer's disease (AD). In the current study, we investigated the ability of SNAP-25 to differentiate between heterogenous dementia etiologies and whether SNAP-25 could be a staging marker in AD. SNAP-25 in the cerebrospinal fluid (CSF) from a retrospective (n = 187) and a prospective (n = 134) cohort was investigated with immunoprecipitation mass spectrometry (IP-MS) and single-molecule array (Simoa), respectively. Both cohorts consisted of healthy controls (HC) and patients with cognitive decline of different etiologies. CSF SNAP-25 concentration was higher in AD and non-neurodegenerative diseases (i.e., vascular dementia) compared with controls but did not differ between AD and non-AD neurodegenerative diseases. We found a trend toward an association between SNAP-25 and disease burden when comparing HC, mild cognitive impairment due to AD, and AD. CSF SNAP-25 concentrations were strongly associated with CSF phosphorylated tau (p-tau) concentrations, thus strengthening the link between synaptic dysfunction and tau pathophysiology in AD. Our initial findings suggest that SNAP-25 may be a potential biomarker for differentiating AD from dementia due to other etiologies. However, due to the significant association between SNAP-25 and p-tau proteins, the clinical utility of SNAP-25 as a diagnostic biomarker for AD may be limited, while SNAP-25 may be useful for monitoring disease progression or treatment response.
Key findings
- CSF SNAP-25 concentration was higher in AD and non-neurodegenerative diseases (i.e., vascular dementia) compared with controls but did not differ between AD and non-AD neurodegenerative diseases.
- We found a trend toward an association between SNAP-25 and disease burden when comparing HC, mild cognitive impairment due to AD, and AD.
- CSF SNAP-25 concentrations were strongly associated with CSF phosphorylated tau (p-tau) concentrations, thus strengthening the link between synaptic dysfunction and tau pathophysiology in AD.
- Our initial findings suggest that SNAP-25 may be a potential biomarker for differentiating AD from dementia due to other etiologies.
- However, due to the significant association between SNAP-25 and p-tau proteins, the clinical utility of SNAP-25 as a diagnostic biomarker for AD may be limited, while SNAP-25 may be useful for monitoring disease progression or treatment response.
Why it matters
This study found that cerebrospinal fluid SNAP-25 was higher in Alzheimer's disease and in non-neurodegenerative diseases such as vascular dementia than in controls, but did not differ between Alzheimer's and non-Alzheimer's neurodegenerative diseases. It suggests SNAP-25 may be a potential biomarker, not a treatment, cure or prevention.
Study details
- Participants187
- Evidence strengthModerate
How this study scored 49/100
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 (Synapse) |
| Journal's citation record | 2 / 4 | Synapse: journal h-index 155 (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 | 187 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 8 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 5.1× 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 8 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Anja Hviid Simonsen: h-index 35 (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 20 institution(s) in 6 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39912369) |
| Free to read | 2 / 2 | Free to read |
| Total | 49 / 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
Wolner, S. H., Gleerup, H. S., Musaeus, C. S., Høgh, P., Ashton, N. J., Brinkmalm, A., et al. (2025). Synaptosomal‐Associated Protein 25 kDA (SNAP‐25) Levels in Cerebrospinal Fluid: Implications for Alzheimer's Disease Diagnosis and Monitoring. Synapse. https://doi.org/10.1002/syn.70010
Vancouver
Wolner SH, Gleerup HS, Musaeus CS, Høgh P, Ashton NJ, Brinkmalm A, et al. Synaptosomal‐Associated Protein 25 kDA (SNAP‐25) Levels in Cerebrospinal Fluid: Implications for Alzheimer's Disease Diagnosis and Monitoring. Synapse. 2025. doi:10.1002/syn.70010. PMID: 39912369.
BibTeX
@article{wolner2025-39912369,
author = {Wolner, Sofia Hjorth and Gleerup, Helena Sophia and Musaeus, Christian Sandøe and Høgh, Peter and Ashton, Nicholas J. and Brinkmalm, Ann and Nilsson, Johanna E. and Grötschel, Lana and others},
title = {{Synaptosomal‐Associated Protein 25 kDA (SNAP‐25) Levels in Cerebrospinal Fluid: Implications for Alzheimer's Disease Diagnosis and Monitoring}},
journal = {Synapse},
year = {2025},
doi = {10.1002/syn.70010},
pmid = {39912369},
url = {https://doi.org/10.1002/syn.70010}
}
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