SV2A is expressed in synapse subpopulations in mouse and human brain: implications for PET radiotracer studies

Synapse pathology is a feature of most brain diseases and there is a pressing need to monitor the onset and progression of this pathology using brain imaging in living patients. A major step toward this goal has been the development of small-molecule radiotracers that bind to synaptic vesicle glycoprotein 2A (SV2A) for use in positron emission tomography (PET). Changes in SV2A radiotracer binding in PET are widely interpreted to report differences in the density of all synapses throughout brain region However, the expression of SV2A at single-synapse level across regions of adult mouse and human brain has not been comprehensively characterised. Here, We employed high-resolution synaptome mapping in adult mouse (n=7) and human (n=3) brain tissue. Synaptic proteins were labelled using fluorescent immunohistochemistry, imaged using confocal microscopy and quantified using image analysis tools. Brain-wide SV2A expression was assessed in presynaptic and postsynaptic terminals.