Abstract:
Synaptic vesicle glycoprotein 2A (SV2A) is a 12 transmembrane protein localized to the membrane of synaptic vesicles. It has attracted significant interest because it is the target for the antiepileptic drug levetiracetam and it is considered a marker for synaptic density also clinically. My laboratory has developed and validated techniques that determine SV2A using radioligand binding (both autoradiography and PET), immunodetection, and expression using quantitative and qualitative methods in single cells and in tissues. We have studied the expression of this protein in patients with epilepsy, Alzheimer’s disease and diabetes, and in corresponding animal models. Animal models of epilepsy are excellent models to study epileptogenesis, because synaptic density is changing over time. SV2A binding is first declining and later increasing consistent with the concept of epileptogenesis. However, change in SV2A concentrations and binding capacity is not always correlated. In the treatment resistant epileptic patient, SV2A expression is found in all types of cortical neurons, and the expression is generally lower or unchanged. Our results show that expression of SV2A and binding of SV2A selective radioligands are not always correlated, which suggest that the dynamics of SV2A in pre-synapse and translocation of vesicles may influence the functionality of SV2A as a drug target and as a biomarker.