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

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 [ ¹¹ C]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 [ ¹¹ C]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 ([ ¹¹ C]UCB‐J) PET was used to quantify synaptic density.

• Reductions of synaptic density were associated with CSF synaptic biomarker levels.