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

TY - UNPB

T1 - SV2A is expressed in synapse subpopulations in mouse and human brain: implications for PET radiotracer studies

AU - Wong, Theresa

AU - Qiu, Zhen

AU - Notman, Beverly

AU - Tavares, Adriana

AU - Smith, Colin

AU - Grant, Seth G.N.

PY - 2024/7/18

Y1 - 2024/7/18

N2 - 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 regions. Here, we analyse the expression of SV2A at single-synapse resolution across regions of adult mouse and human brain. We find that SV2A is expressed in fewer than 50% of excitatory and inhibitory synapses and that the density of SV2A-positive synapses differs between brain regions. Furthermore, individual synapses differ in their amounts of SV2A. These findings have important implications for the interpretation of PET imaging studies in a clinical setting and point to the need for a detailed understanding of SV2A synaptome architecture in both healthy brain and disease cases where PET imaging is being applied.

AB - 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 regions. Here, we analyse the expression of SV2A at single-synapse resolution across regions of adult mouse and human brain. We find that SV2A is expressed in fewer than 50% of excitatory and inhibitory synapses and that the density of SV2A-positive synapses differs between brain regions. Furthermore, individual synapses differ in their amounts of SV2A. These findings have important implications for the interpretation of PET imaging studies in a clinical setting and point to the need for a detailed understanding of SV2A synaptome architecture in both healthy brain and disease cases where PET imaging is being applied.

KW - Positron Emission Tomography

KW - synaptome

KW - presynaptic terminal

KW - synapse diversity

U2 - 10.1101/2024.07.15.603608

DO - 10.1101/2024.07.15.603608

M3 - Preprint

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

PB - BioRxiv

ER -