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bioRxiv · 10.1101/2025.03.31.646290

Associations between fluid biomarkers and PET imaging (UCB-J) of synaptic pathology in Alzheimer's disease

Nilsson, J.·Mecca, A.·Ashton, N. J.·Salardini, E.·Odell, R.·Carson, R.·Benedet, A.·Blennow, K.·Zetterberg, H.·Van Dyck, C.·Brinkmalm, A.
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Abstract

INTRODUCTIONPositron Emission Tomography (PET) imaging with ligands for synaptic vesicle glycoprotein 2A (SV2A) has emerged as a promising methodology for measuring synaptic density in Alzheimers disease (AD). We investigate the relationship between SV2A PET and CSF synaptic protein changes of AD patients. METHODTwenty-one participants with early AD and 7 cognitively normal (CN) individuals underwent [11C]UCB-J PET. We used mass spectrometry to measure a panel of synaptic proteins in CSF. RESULTSIn 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, {gamma}-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. CONCLUSIONReductions of synaptic density found in AD compared to CN participants using [11C]UCB-J PET were observed to be associated with CSF biomarker levels of synaptic proteins.

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Nilsson, J., Mecca, A., Ashton, N. J., Salardini, E., Odell, R., Carson, R., Benedet, A., Blennow, K., Zetterberg, H., Van Dyck, C., Brinkmalm, A.. 2025-04-05. Associations between fluid biomarkers and PET imaging (UCB-J) of synaptic pathology in Alzheimer's disease. https://doi.org/10.1101/2025.03.31.646290

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