Associations between fluid biomarkers and PET imaging ([ 11 C]UCB-J) of synaptic pathology in Alzheimer’s disease

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INTRODUCTION Positron Emission Tomography (PET) imaging with ligands for synaptic vesicle glycoprotein 2A (SV2A) has emerged as a promising methodology for measuring synaptic density in Alzheimer’s disease (AD). We investigate the relationship between SV2A PET and CSF synaptic protein changes of AD patients. METHOD Twenty-one participants with early AD and 7 cognitively normal (CN) individuals underwent [ 11 C]UCB-J PET. We used mass spectrometry to measure a panel of synaptic proteins in CSF. RESULTS In the AD group, higher levels of syntaxin-7 and PEBP-1 were associated with lower global synaptic density. In the total sample, lower global synaptic density was associated with higher levels of AP2B1, neurogranin, γ-synuclein, GDI-1, PEBP-1, syntaxin-1B, and syntaxin-7 but not with the levels of the neuronal pentraxins or 14-3-3 zeta/delta. CONCLUSION Reductions of synaptic density found in AD compared to CN participants using [ 11 C]UCB-J PET were observed to be associated with CSF biomarker levels of synaptic proteins.