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

Abstract

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 investigated the relationship between SV2A PET and CSF synaptic protein changes of AD patients.

Method: Twenty-one participants with early AD and seven cognitively normal (CN) individuals underwent [¹¹C]UCB-J PET. We used mass spectrometry to measure a panel of synaptic proteins in cerebrospinal fluid (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 [¹¹C]UCB-J PET were observed to be associated with CSF biomarker levels of synaptic proteins.

Highlights: A panel of synaptic proteins was quantified in the CSF using mass spectrometry. SV2A ([¹¹C]UCB-J) PET was used to quantify synaptic density. Reductions of synaptic density were associated with CSF synaptic biomarker levels.

Keywords: Alzheimer's disease; SV2A; biomarkers; mass spectrometry; synaptic pathology.