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Serum level changes of the synaptic marker beta-synuclein in Alzheimer’s disease continuum and other dementias
Lorenzo Barba, Giovanni Bellomo, Daniel Andres Alcolea, Anna Lidia Wojdała, Lorenzo Gaetani, Juan Fortea, Samir Abu‐Rumeileh, Alberto Lleó et al.. Journal of Neurology Neurosurgery & Psychiatry, 2025-06-26
Topic: Amyloid, tau and blood-test diagnosis
Serum beta-synuclein level was progressively increased in the AD continuum across the preclinical, MCI and dementia stages compared with controls and was correlated with serum pTau181 (r=0.710), NfL (r=0.494) and GFAP concentrations (r=0.621, p<0.001 for all). The biomarker showed high accuracy for the discrimination of AD vs controls (area under the curve (AUC): 0.87) and AD-MCI vs non-AD MCI (AUC: 0.96). High serum beta-synuclein level was correlated with lower Mini-Mental State Examination (MMSE) points at baseline (r=-0.461, p<0.001) and associated with MMSE change at follow-up after accounting for age, sex and the time from baseline to last follow-up visit (p=0.006). Serum beta-synuclein level was similar between FTLD and controls, whereas, in LBD, it was higher with AD copathology as evidenced by CSF analysis (p<0.001). High serum beta-synuclein level is a promising biomarker for AD-related synaptic damage.
Key findings
- Serum beta-synuclein level was progressively increased in the AD continuum across the preclinical, MCI and dementia stages compared with controls and was correlated with serum pTau181 (r=0.710), NfL (r=0.494) and GFAP concentrations (r=0.621, p<0.001 for all).
- The biomarker showed high accuracy for the discrimination of AD vs controls (area under the curve (AUC): 0.87) and AD-MCI vs non-AD MCI (AUC: 0.96).
- High serum beta-synuclein level was correlated with lower Mini-Mental State Examination (MMSE) points at baseline (r=-0.461, p<0.001) and associated with MMSE change at follow-up after accounting for age, sex and the time from baseline to last follow-up visit (p=0.006).
- Serum beta-synuclein level was similar between FTLD and controls, whereas, in LBD, it was higher with AD copathology as evidenced by CSF analysis (p<0.001).
- High serum beta-synuclein level is a promising biomarker for AD-related synaptic damage.
Why it matters
Blood levels of beta-synuclein rose step by step across the stages of Alzheimer's disease and distinguished Alzheimer's from controls with high accuracy. This is a promising biomarker for Alzheimer's-related damage to brain connections, but it is not yet a treatment or a cure.
Study details
- Participants56
- Effect sizeAUC: 0.96
- Evidence strengthModerate
How this study scored 46/100
Published in a peer-reviewed journal. Scored zero for study design and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Neurology Neurosurgery & Psychiatry) |
| Journal's citation record | 3 / 4 | Journal of Neurology Neurosurgery & Psychiatry: journal h-index 336 (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 | 1 / 4 | 56 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 Patrick Oeckl: h-index 42 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Perugia: institution h-index 747 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40571405) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 46 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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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
Barba, L., Bellomo, G., Alcolea, D. A., Wojdała, A. L., Gaetani, L., Fortea, J., et al. (2025). Serum level changes of the synaptic marker beta-synuclein in Alzheimer’s disease continuum and other dementias. Journal of Neurology Neurosurgery & Psychiatry. https://doi.org/10.1136/jnnp-2025-336189
Vancouver
Barba L, Bellomo G, Alcolea DA, Wojdała AL, Gaetani L, Fortea J, et al. Serum level changes of the synaptic marker beta-synuclein in Alzheimer’s disease continuum and other dementias. Journal of Neurology Neurosurgery & Psychiatry. 2025. doi:10.1136/jnnp-2025-336189. PMID: 40571405.
BibTeX
@article{barba2025-40571405,
author = {Barba, Lorenzo and Bellomo, Giovanni and Alcolea, Daniel Andres and Wojdała, Anna Lidia and Gaetani, Lorenzo and Fortea, Juan and Abu‐Rumeileh, Samir and Lleó, Alberto and others},
title = {{Serum level changes of the synaptic marker beta-synuclein in Alzheimer’s disease continuum and other dementias}},
journal = {Journal of Neurology Neurosurgery \& Psychiatry},
year = {2025},
doi = {10.1136/jnnp-2025-336189},
pmid = {40571405},
url = {https://doi.org/10.1136/jnnp-2025-336189}
}
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