Journal Article

DZNE-2026-01117

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Plasma β-synuclein associates with hippocampal synaptic density measured with [11C]UCB-J PET and plasma tau markers in Alzheimer's disease.

Peter, D. C. ; McLachlan, M. ; DiFilippo, A. H. ; Yang, K. L. ; Pasquesi, M.-E. ; Barnhart, T. E. ; Engle, J. W. ; Betthauser, T. J. ; Asthana, S. ; Johnson, S. C. ; Christian, B. T. ; Bendlin, B. B. ; Otto, M. ; Oeckl, P. (Last author)DZNE*

2026
Wiley Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/alz.71900

Abstract: Plasma β-synuclein is a promising blood-based synaptic biomarker, but relationships with synaptic density as indicated by [11C]UCB-J positron emission tomography (PET), and blood biomarkers of Alzheimer's disease (AD) pathology, neurodegeneration, and astrocyte activation need further characterization.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]).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.This work further supports utilization of plasma β-synuclein to track synaptic degeneration in AD.

Keyword(s): Humans (MeSH) ; Alzheimer Disease: blood (MeSH) ; Alzheimer Disease: diagnostic imaging (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Positron-Emission Tomography (MeSH) ; Female (MeSH) ; Male (MeSH) ; tau Proteins: blood (MeSH) ; Aged (MeSH) ; Biomarkers: blood (MeSH) ; Hippocampus: diagnostic imaging (MeSH) ; Hippocampus: pathology (MeSH) ; Hippocampus: metabolism (MeSH) ; Synapses: pathology (MeSH) ; Synapses: metabolism (MeSH) ; Middle Aged (MeSH) ; beta-Synuclein: blood (MeSH) ; Glial Fibrillary Acidic Protein: blood (MeSH) ; Neuropsychological Tests (MeSH) ; Cognitive Dysfunction: blood (MeSH) ; Cognitive Dysfunction: diagnostic imaging (MeSH) ; Carbon Radioisotopes (MeSH) ; Pyridines (MeSH) ; Alzheimer's disease ; [11C]UCB‐J PET ; beta‐synuclein ; blood‐based biomarkers ; synaptic density ; tau Proteins ; Biomarkers ; beta-Synuclein ; Glial Fibrillary Acidic Protein ; Carbon Radioisotopes ; Pyridines

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Contributing Institute(s):

1. Translational Mass Spectrometry and Biomarker Research (AG Öckl)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Wiley ; Essential Science Indicators ; IF >= 10 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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