Plasma β‐synuclein associates with hippocampal synaptic density measured with [ 11 C]UCB‐J PET and plasma tau markers in Alzheimer's disease
Darby C Peter, Max McLachlan, Alexandra H DiFilippo, Kao Lee Yang, Mary‐Elizabeth Pasquesi, Todd E Barnhart, Jonathan W Engle, Tobey J Betthauser, Sanjay Asthana, Sterling C Johnson, Bradley T Christian, Barbara B Bendlin, Markus Otto, Patrick OecklAbstract
INTRODUCTION
Plasma β‐synuclein is a promising blood‐based synaptic biomarker, but relationships with synaptic density as indicated by [ 11 C]UCB‐J positron emission tomography (PET), and blood biomarkers of Alzheimer's disease (AD) pathology, neurodegeneration, and astrocyte activation need further characterization.
METHODS
Middle‐aged and older adults with and without cognitive impairment ( N = 83 total, 68.7% cognitively unimpaired) underwent blood draw, PET imaging, and neuropsychological testing. Primary analyses focused on relationships between plasma β‐synuclein and synaptic density, and associations with related plasma biomarkers (tau phosphorylated at threonine 217 [p‐tau217], brain‐derived tau [BD‐tau], glial fibrillary acidic protein [GFAP], and neurofilament light chain [NfL]).
RESULTS
Plasma β‐synuclein levels were higher in cognitively unimpaired and impaired participants with positive amyloid PET. Synaptic density was lower in cognitively impaired participants only. In the full sample, higher plasma β‐synuclein levels associated with lower synaptic density in the hippocampus, higher concentrations of plasma tau markers, and higher plasma GFAP.
DISCUSSION
This work further supports utilization of plasma β‐synuclein to track synaptic degeneration in AD.