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Synaptic vesicle glycoprotein 2A PET imaging in parkinsonian α-synucleinopathies: a systematic review
Garrou F, Leva L, Sacchetti GM, De Natale ER, Tondo G, Comi C.. Journal of neurology, 2026-09-07
Topic: Brain proteins, microglia and lab models
Synaptic dysfunction is increasingly recognized as an early and biologically relevant component of α-synucleinopathies. However, conventional imaging biomarkers mainly assess dopaminergic dysfunction, glucose metabolism, or structural damage rather than presynaptic density itself. Synaptic vesicle glycoprotein 2A (SV2A) PET enables in vivo assessment of presynaptic terminal integrity and may provide complementary information in Parkinson's disease (PD), Parkinson's disease dementia/dementia with Lewy bodies (PDD/DLB), and multiple system atrophy (MSA). This systematic review synthesized the available evidence on SV2A-targeted PET in parkinsonian α-synucleinopathies, focusing on regional imaging patterns, clinical associations, longitudinal findings, and methodological determinants of interpretation. Seventeen reports were included. In PD, the most recurrent finding was reduced SV2A binding in the substantia nigra, although additional involvement of brainstem, caudate, striatal, thalamic, raphe, or cortical regions was reported in selected cohorts. In PDD/DLB, abnormalities appeared broader and more cortical, with evidence of association between cortical SV2A binding and cognitive performance. In MSA, one study suggested a distinct infratentorial and cerebellar pattern with potential relevance for phenotypic stratification. SV2A PET is a promising research biomarker for biological characterization of synucleinopathies. However, the field remains limited by small cohorts, methodological heterogeneity, variable quantification strategies, limited longitudinal evidence, and potential cohort overlap. Multicentre validation and harmonized protocols are required before clinical translation.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Garrou, F., Leva, L., Sacchetti, G. M., De Natale, E. R., Tondo, G., & Comi, C. (2026). Synaptic vesicle glycoprotein 2A PET imaging in parkinsonian α-synucleinopathies: a systematic review. Journal of neurology. https://doi.org/10.1007/s00415-026-14123-2
Vancouver
Garrou F, Leva L, Sacchetti GM, De Natale ER, Tondo G, Comi C. Synaptic vesicle glycoprotein 2A PET imaging in parkinsonian α-synucleinopathies: a systematic review. Journal of neurology. 2026. doi:10.1007/s00415-026-14123-2. PMID: 42704496.
BibTeX
@article{garrou2026-42704496,
author = {Garrou, F. and Leva, L. and Sacchetti, G. M. and De Natale, E. R. and Tondo, G. and Comi, C.},
title = {{Synaptic vesicle glycoprotein 2A PET imaging in parkinsonian α-synucleinopathies: a systematic review}},
journal = {Journal of neurology},
year = {2026},
doi = {10.1007/s00415-026-14123-2},
pmid = {42704496},
url = {https://doi.org/10.1007/s00415-026-14123-2}
}
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.
Key findings
- In PDD/DLB, abnormalities appeared broader and more cortical, with evidence of association between cortical SV2A binding and cognitive performance.
- In MSA, one study suggested a distinct infratentorial and cerebellar pattern with potential relevance for phenotypic stratification.
- SV2A PET is a promising research biomarker for biological characterization of synucleinopathies.
- However, the field remains limited by small cohorts, methodological heterogeneity, variable quantification strategies, limited longitudinal evidence, and potential cohort overlap.
- Multicentre validation and harmonized protocols are required before clinical translation.
Why it matters
This systematic review pulled together seventeen reports using SV2A PET, a scan that measures the density of nerve-cell connections (synapses), in Parkinson's disease, Parkinson's disease dementia/dementia with Lewy bodies and multiple system atrophy. Parkinson's disease most often showed reduced binding in the substantia nigra, while Parkinson's disease dementia and dementia with Lewy bodies showed broader, more cortical changes linked to cognitive performance. The authors see it as a promising research tool, but say small cohorts and inconsistent methods mean it is not ready for clinical use.
Study details
- Study designsystematic review
- Evidence strengthHigh
How this study scored 48/100
Published in a peer-reviewed journal, and it is a systematic review of all the studies on the question. Scored zero for sample size, effect reported and studied in people because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neurology) |
| Journal's citation record | 2 / 4 | Journal of Neurology: journal h-index 208 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A systematic review of all the studies on the question |
| Strength of evidence | 5 / 5 | Rated “high” 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 | A review of other studies — randomisation is not credited here |
| Times cited | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 0 / 6 | Cited 0.0× 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 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Cristoforo Comi: h-index 46 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Exeter: institution h-index 905 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42704496) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 48 / 100 | — |
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