SV2A


Synaptic vesicle glycoprotein 2A is a transmembrane protein belonging to a family of keratan sulfate proteoglycans, located on the synaptic vesicles of mammalian neuronal and endocrine cells. It is encoded by the SV2A gene.
SV2A is the most widely expressed isoform of the SV2 family found in all brain regions. The role of the SV2 proteins is not well understood; however, they are thought to be involved in regulating vesicular processes.
The SV2A protein is a target of the anti-epileptic drugs levetiracetam and brivaracetam but it is not clear how these drug affect SV2A activity.

Localisation

SV2A is differentially expressed in both inhibitory GABAergic and excitatory glutamatergic terminals however it is not expressed in all synapses as was previously thought. There is a slightly stronger colocalisation between SV2A and GABA than glutamate and the association differs across brain regions and changes with developmental stages.

SV2A PET

Several PET radiotracers targeting SV2A have been developed, allowing for measuring SV2A density in-vivo: LEV, UCB-A, -UCB-H, UCB-J, Syn-VesT-1, Syn-VesT-2, and SDM-16. SV2A density has been used as a proxy for measuring in vivo synaptic density.
A 2024 systematic review and meta-analysis of UCB-J PET studies reported lower SV2A binding in individuals with psychotic disorders compared with healthy controls.