SV2A PET imaging in Parkinson's disease and atypical parkinsonism: A systematic review of neuroimaging methodologies and regional findings

Background Reduced presynaptic density, commonly referred to as synaptic loss, is an early and clinically relevant feature of parkinsonian disorders. The development of positron emission tomography (PET) radiotracers targeting synaptic vesicle glycoprotein 2A (SV2A) has enabled in vivo quantification of synaptic density. Objectives This systematic review examines neuroimaging methodologies and regional SV2A PET findings in Parkinson's disease (PD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and multiple system atrophy (MSA). Methods A systematic search of PubMed, Scopus, and Web of Science was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines, including studies employing validated SV2A PET radiotracers to quantify synaptic density in parkinsonian populations. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. Substantial methodological heterogeneity precluded meta-analysis; findings were synthesized narratively. Results Fourteen studies were included. In PD, the substantia nigra was the most affected region, with striatal involvement more prominent in advanced disease (>6 years duration). In PSP and CBD, synaptic loss was widespread, exceeded grey matter atrophy, and correlated with clinical severity and cognitive decline; longitudinal PSP data showed reductions of approximately 3–4% per year in frontal and caudate regions. In MSA, infratentorial involvement (cerebellum, pons, medulla) predominated, enabling diagnostic differentiation with high accuracy (AUC up to 0.99). Conclusions SV2A PET reveals disease-specific patterns of reduced presynaptic availability, consistent with synaptic loss, across parkinsonian disorders, supporting its potential as a diagnostic and monitoring biomarker. Methodological harmonization and longitudinal multicenter studies are needed to establish clinical utility.