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Synaptic loss in alcohol use disorder: clinical and mechanistic insights from a PET imaging study
Sarah K. Royse, R Narendran. Journal of Clinical Investigation, 2026-03-31
Topic: Brain proteins, microglia and lab models
Alcohol use disorder (AUD) is linked with changes in brain structure and function, with robust evidence for neurodegenerative changes, including synaptic loss in preclinical models. Developing therapeutic strategies to target synaptic loss will require human studies that clarify their clinical relevance of these changes. In the current issue, Zakiniaeiz et al. demonstrate that AUD and alcohol consumption are associated with lower synaptic vesicle glycoprotein 2a (SV2A) expression, indexed by regional [11C]UCB-J PET. This is, to our knowledge, the first in vivo evidence of relationships between synaptic density and alcohol use, and, as such, it represents an important step toward understanding how AUD influences brain structure and function. Here, we describe two longstanding clinical issues in the AUD population - relapse and dementia risk - and how the results of the present study may guide future investigations of these issues.
Key findings
- In the current issue, Zakiniaeiz et al. demonstrate that AUD and alcohol consumption are associated with lower synaptic vesicle glycoprotein 2a (SV2A) expression, indexed by regional [11C]UCB-J PET.
- Here, we describe two longstanding clinical issues in the AUD population - relapse and dementia risk - and how the results of the present study may guide future investigations of these issues.
Why it matters
This is the first in vivo evidence linking synaptic density to alcohol use, showing that alcohol use disorder and alcohol consumption are associated with lower SV2A expression. The authors say this may guide future research into relapse and dementia risk in people with alcohol use disorder, but no treatment or prevention is tested here.
Study details
- Evidence strengthLow
How this study scored 38/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 36 of the 96 points we could judge it on, which is 38 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Clinical Investigation) |
| Journal's citation record | 4 / 4 | Journal of Clinical Investigation: journal h-index 706 (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 | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 3 / 6 | Cited 4.5× 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 | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author R Narendran holds only 2 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 1 / 3 | University of Pittsburgh: institution h-index 1,470 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41919494) |
| Free to read | 2 / 2 | Free to read |
| Points | 36 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 36 of the 96 points we could judge it on is 38 out of 100. |
| Total | 38 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1172/jci204460
- PubMed: 41919494
- Original source →
- Free full text: Journal of Clinical Investigation →
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. Check the citation against the original before you use it.
APA 7th
Royse, S. K., & Narendran, R. (2026). Synaptic loss in alcohol use disorder: clinical and mechanistic insights from a PET imaging study. Journal of Clinical Investigation. https://doi.org/10.1172/jci204460
Vancouver
Royse SK, Narendran R. Synaptic loss in alcohol use disorder: clinical and mechanistic insights from a PET imaging study. Journal of Clinical Investigation. 2026. doi:10.1172/jci204460. PMID: 41919494.
BibTeX
@article{royse2026-41919494,
author = {Royse, Sarah K. and Narendran, R},
title = {{Synaptic loss in alcohol use disorder: clinical and mechanistic insights from a PET imaging study}},
journal = {Journal of Clinical Investigation},
year = {2026},
doi = {10.1172/jci204460},
pmid = {41919494},
url = {https://doi.org/10.1172/jci204460}
}
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