A number of proteins expressed in presynaptic terminals and the postsynaptic density are used as markers of synaptic density. Synaptophysin is the most studied presynaptic protein, and an accurate index of neuronal synaptic density because it is limited to neuronal synapses.1
Synaptophysin is enriched in presynaptic nerve terminals where, along with SV2A, it is involved in regulating vesicle exocytosis into synapses. A PET radiotracer specific for SV2A permits in vivo investigation of it as a marker of presynaptic protein density.1
Abbreviations: PET=positron emission tomography; SV2A=synaptic protein 2A
References:
1. Osimo EF, Beck K, Reis Marques T, et al. Synaptic loss in schizophrenia: a meta-analysis and systematic review of synaptic protein and mRNA measures. Mol Psychiatry 2019; 24: 549–561.
2. Fish KN, Sweet RA, MacDonald ML, Lewis DA. Regional specificity of cortical layer 3 dendritic spine deficits in schizophrenia. JAMA Psychiatry 2025; 82: 1123–1132.
3. Onwordi EC, Halff EF, Whitehurst T, et al. Synaptic density marker SV2A is reduced in schizophrenia patients and unaffected by antipsychotics in rats. Nat Commun 2020; 11: 246.
4. Howes OD, Cummings C, Chapman GE, et al. Neuroimaging in schizophrenia: an overview of findings and their implications for synaptic changes. Neuropsychopharmacology 2023; 48: 151–167.