Development of an imaging marker for synaptic vesicular glycoprotein SV2C: a specific target for synaptic density in Parkinson´s disease

Synaptic dysfunction is an early event in the natural history of Parkinson´s disease (PD) and is linked to the development of α-synuclein pathology. These changes ultimately result in loss of synapses and neuronal degeneration. The vescicular glycoprotein SV2C is a synaptic protein highly expressed in the basal ganglia system.

The protein has a role in regulating dopamine release and synaptic transmission. Initial studies showed that SV2C is impaired in animal models of PD and in brain tissue from PD patients.

In view of its distribution and specific role in the basal ganglia, SV2C might be a specific marker to study the synaptopathy in PD and a potential imaging target to assess disease progression and effects of disease-modifying treatments.Our hypothesis is that the loss of SV2C is associated with α-synuclein pathology.

To test this hypothesis, we will use a unique rodent PD model of synucleinopathy that displays characteristic abnormalities observed in human disease. We will first develop a specific imaging marker for SV2C.

Then we will use molecular imaging with positron emission tomography and autoradiography, to examine the loss of SV2C in relation to the accumulation of α-synuclein and to the severity of the dopaminergic degeneration.

Imaging will be complemented with the measurement of SV2A as global marker of synaptic density and of dopamine transporter (DAT) as dopaminergic marker.