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@ARTICLE{Barba:282296,
author = {Barba, Lorenzo and Bellomo, Giovanni and Alcolea, Daniel
and Wojdala, Anna L and Gaetani, Lorenzo and Fortea, Juan
and Abu-Rumeileh, Samir and Lleó, Alberto and Parnetti,
Lucilla and Belbin, Olivia and Otto, Markus and Oeckl,
Patrick},
title = {{S}erum level changes of the synaptic marker beta-synuclein
in {A}lzheimer's disease continuum and other dementias.},
journal = {Journal of neurology, neurosurgery, and psychiatry},
volume = {96},
number = {12},
issn = {0022-3050},
address = {London},
publisher = {BMJ Publishing Group},
reportid = {DZNE-2025-01266},
pages = {1144 - 1153},
year = {2025},
abstract = {Beta-synuclein is an emerging blood biomarker for detecting
synaptic damage in Alzheimer's disease (AD) but its role in
early AD as well as in other dementias is unclear.We
measured with immunoprecipitation mass-spectrometry serum
beta-synuclein levels in an exploratory cohort of 80
patients recruited at the University of Perugia (Perugia,
Italy) (n=56 AD; n=24 controls) and in a validation cohort
of 269 patients recruited at the University of Barcelona
(Barcelona, Spain) (n=108 AD; n=53 frontotemporal lobar
degeneration (FTLD); n=73 dementia with Lewy bodies and mild
cognitive impairment (MCI) with Lewy bodies, together Lewy
body disease (LBD); n=27 controls). We tested associations
with diagnostic groups, cognitive decline and other
cerebrospinal fluid (CSF) and blood markers (phosphorylated
tau protein in position 181 (pTau181), neurofilament light
chain protein (NfL), glial fibrillar acidic protein
(GFAP)).Serum beta-synuclein level was progressively
increased in the AD continuum across the preclinical, MCI
and dementia stages compared with controls and was
correlated with serum pTau181 (r=0.710), NfL (r=0.494) and
GFAP concentrations (r=0.621, p<0.001 for all). The
biomarker showed high accuracy for the discrimination of AD
vs controls (area under the curve (AUC): 0.87) and AD-MCI vs
non-AD MCI (AUC: 0.96). High serum beta-synuclein level was
correlated with lower Mini-Mental State Examination (MMSE)
points at baseline (r=-0.461, p<0.001) and associated with
MMSE change at follow-up after accounting for age, sex and
the time from baseline to last follow-up visit (p=0.006).
Serum beta-synuclein level was similar between FTLD and
controls, whereas, in LBD, it was higher with AD copathology
as evidenced by CSF analysis (p<0.001).High serum
beta-synuclein level is a promising biomarker for AD-related
synaptic damage.},
keywords = {Humans / Male / Female / Alzheimer Disease: blood /
Alzheimer Disease: cerebrospinal fluid / Aged / Biomarkers:
blood / Lewy Body Disease: blood / Lewy Body Disease:
cerebrospinal fluid / Cognitive Dysfunction: blood /
Cognitive Dysfunction: cerebrospinal fluid / tau Proteins:
blood / tau Proteins: cerebrospinal fluid / beta-Synuclein:
blood / Aged, 80 and over / Frontotemporal Lobar
Degeneration: blood / Frontotemporal Lobar Degeneration:
cerebrospinal fluid / Middle Aged / Neurofilament Proteins:
blood / Neurofilament Proteins: cerebrospinal fluid / Glial
Fibrillary Acidic Protein: blood / Glial Fibrillary Acidic
Protein: cerebrospinal fluid / Dementia: blood / Cohort
Studies / ALZHEIMER'S DISEASE (Other) / FRONTOTEMPORAL
DEMENTIA (Other) / LEWY BODY DEMENTIA (Other) /
NEUROCHEMISTRY (Other) / Biomarkers (NLM Chemicals) / tau
Proteins (NLM Chemicals) / beta-Synuclein (NLM Chemicals) /
neurofilament protein L (NLM Chemicals) / Neurofilament
Proteins (NLM Chemicals) / Glial Fibrillary Acidic Protein
(NLM Chemicals)},
cin = {AG Öckl},
ddc = {610},
cid = {I:(DE-2719)5000073},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40571405},
doi = {10.1136/jnnp-2025-336189},
url = {https://pub.dzne.de/record/282296},
}