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Peer-reviewedCC BY-NC 4.0Molecular Diagnosis & Therapy

Mapping the Synaptome in Neurodegeneration: Emerging Clinical Applications of SV2A PET Imaging

  • Luca Filippi1,2
  • Susanna Nuvoli3
  • Angela Spanu3
  • Barbara Palumbo4,5
5 affiliations
  1. 1Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier, 1, 00133 Rome, Italy
  2. 2Nuclear Medicine Research Unit, IRCCS San Raffaele Roma, Rome, Italy
  3. 3Unit of Nuclear Medicine, Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy
  4. 4Section of Nuclear Medicine and Health Physics, Department of Medicine and Surgery, Università degli Studi di Perugia, Perugia, Italy
  5. 5Nuclear Medicine Division, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, Perugia, Italy
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Abstract

Synaptic loss is a core pathological feature of neurodegenerative disorders and closely relates to cognitive and functional decline. Positron emission tomography (PET) targeting synaptic vesicle glycoprotein 2A (SV2A) has recently emerged as a promising tool for the indirect assessment of presynaptic alterations in the living human brain. This leading article discusses the evolving clinical landscape of SV2A PET across the neurodegenerative spectrum, emphasizing its translational trajectory and emerging applications. Current evidence spans Alzheimer’s disease (AD), other dementias, movement disorders, Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). The literature is currently dominated by PET with [11C]UCB-J, while [18F]-labeled tracers, particularly [18F]SynVesT-1, are expanding clinical feasibility through longer half-life and broader distribution potential. Across disorders, PET consistently detected SV2A reductions that frequently correlated with cognition, disease severity, and complementary biomarkers, including amyloid, tau, glucose metabolism, and dopaminergic imaging. Although the field remains limited by small cohorts, heterogeneous quantification strategies, and incomplete longitudinal validation, SV2A PET is rapidly evolving into a promising translational tool for studying synaptopathies and monitoring disease progression.

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Cite

BibTeXRIS
BibTeX
@article{filippi2026mapping,
  title = {{Mapping the Synaptome in Neurodegeneration: Emerging Clinical Applications of SV2A PET Imaging}},
  author = {Luca Filippi and Susanna Nuvoli and Angela Spanu and Barbara Palumbo},
  journal = {Molecular Diagnosis \& Therapy},
  year = {2026},
  month = aug,
  doi = {10.1007/s40291-026-00871-4},
  url = {https://doi.org/10.1007/s40291-026-00871-4},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Mapping the Synaptome in Neurodegeneration: Emerging Clinical Applications of SV2A PET Imaging
AU  - Luca Filippi
AU  - Susanna Nuvoli
AU  - Angela Spanu
AU  - Barbara Palumbo
PY  - 2026
DA  - 2026/08/11
JO  - Molecular Diagnosis & Therapy
DO  - 10.1007/s40291-026-00871-4
UR  - https://doi.org/10.1007/s40291-026-00871-4
AB  - Synaptic loss is a core pathological feature of neurodegenerative disorders and closely relates to cognitive and functional decline. Positron emission tomography (PET) targeting synaptic vesicle glycoprotein 2A (SV2A) has recently emerged as a promising tool for the indirect assessment of presynaptic alterations in the living human brain. This leading article discusses the evolving clinical landscape of SV2A PET across the neurodegenerative spectrum, emphasizing its translational trajectory and emerging applications. Current evidence spans Alzheimer’s disease (AD), other dementias, movement disorders, Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). The literature is currently dominated by PET with [11C]UCB-J, while [18F]-labeled tracers, particularly [18F]SynVesT-1, are expanding clinical feasibility through longer half-life and broader distribution potential. Across disorders, PET consistently detected SV2A reductions that frequently correlated with cognition, disease severity, and complementary biomarkers, including amyloid, tau, glucose metabolism, and dopaminergic imaging. Although the field remains limited by small cohorts, heterogeneous quantification strategies, and incomplete longitudinal validation, SV2A PET is rapidly evolving into a promising translational tool for studying synaptopathies and monitoring disease progression.
SN  - 1177-1062
SN  - 1179-2000
ER  -