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Synaptic vesicle glycoprotein 2A PET imaging in parkinsonian α-synucleinopathies: a systematic review.

Federico Garrou·Lucia Leva·Gian Mauro Sacchetti·Edoardo Rosario De Natale·Giacomo Tondo·Cristoforo Comi
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Abstract

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.

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HumansBrainLewy Body DiseaseMembrane GlycoproteinsMultiple System AtrophyNerve Tissue ProteinsParkinson DiseaseParkinsonian DisordersPositron-Emission TomographySynucleinopathiesDementia with Lewy bodiesMultiple system atrophyParkinson’s diseaseSV2A PETSynaptic vesicle glycoprotein 2Aα-SynucleinopathiesJournal ArticleSystematic ReviewReview

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Federico Garrou, Lucia Leva, Gian Mauro Sacchetti, Edoardo Rosario De Natale, Giacomo Tondo, Cristoforo Comi. 2026-09-07. Synaptic vesicle glycoprotein 2A PET imaging in parkinsonian α-synucleinopathies: a systematic review.. https://doi.org/10.1007/s00415-026-14123-2

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Brain subjectHumans subjectJournal Article subjectJournal Article; Systematic Review; Review resourceMembrane Glycoproteins subjectParkinson Disease subjectParkinson’s disease subjectParkinsonian disorders subjectPositron-Emission Tomography subjectSystematic reviews study

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