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000282296 0247_ $$2ISSN$$a2753-0477
000282296 0247_ $$2ISSN$$a2753-0485
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000282296 041__ $$aEnglish
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000282296 1001_ $$00000-0003-1328-3620$$aBarba, Lorenzo$$b0
000282296 245__ $$aSerum level changes of the synaptic marker beta-synuclein in Alzheimer's disease continuum and other dementias.
000282296 260__ $$aLondon$$bBMJ Publishing Group$$c2025
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000282296 520__ $$aBeta-synuclein is an emerging blood biomarker for detecting synaptic damage in Alzheimer's disease (AD) but its role in early AD as well as in other dementias is unclear.We measured with immunoprecipitation mass-spectrometry serum beta-synuclein levels in an exploratory cohort of 80 patients recruited at the University of Perugia (Perugia, Italy) (n=56 AD; n=24 controls) and in a validation cohort of 269 patients recruited at the University of Barcelona (Barcelona, Spain) (n=108 AD; n=53 frontotemporal lobar degeneration (FTLD); n=73 dementia with Lewy bodies and mild cognitive impairment (MCI) with Lewy bodies, together Lewy body disease (LBD); n=27 controls). We tested associations with diagnostic groups, cognitive decline and other cerebrospinal fluid (CSF) and blood markers (phosphorylated tau protein in position 181 (pTau181), neurofilament light chain protein (NfL), glial fibrillar acidic protein (GFAP)).Serum beta-synuclein level was progressively increased in the AD continuum across the preclinical, MCI and dementia stages compared with controls and was correlated with serum pTau181 (r=0.710), NfL (r=0.494) and GFAP concentrations (r=0.621, p<0.001 for all). The biomarker showed high accuracy for the discrimination of AD vs controls (area under the curve (AUC): 0.87) and AD-MCI vs non-AD MCI (AUC: 0.96). High serum beta-synuclein level was correlated with lower Mini-Mental State Examination (MMSE) points at baseline (r=-0.461, p<0.001) and associated with MMSE change at follow-up after accounting for age, sex and the time from baseline to last follow-up visit (p=0.006). Serum beta-synuclein level was similar between FTLD and controls, whereas, in LBD, it was higher with AD copathology as evidenced by CSF analysis (p<0.001).High serum beta-synuclein level is a promising biomarker for AD-related synaptic damage.
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000282296 650_7 $$2Other$$aALZHEIMER'S DISEASE
000282296 650_7 $$2Other$$aFRONTOTEMPORAL DEMENTIA
000282296 650_7 $$2Other$$aLEWY BODY DEMENTIA
000282296 650_7 $$2Other$$aNEUROCHEMISTRY
000282296 650_7 $$2NLM Chemicals$$aBiomarkers
000282296 650_7 $$2NLM Chemicals$$atau Proteins
000282296 650_7 $$2NLM Chemicals$$abeta-Synuclein
000282296 650_7 $$2NLM Chemicals$$aneurofilament protein L
000282296 650_7 $$2NLM Chemicals$$aNeurofilament Proteins
000282296 650_7 $$2NLM Chemicals$$aGlial Fibrillary Acidic Protein
000282296 650_2 $$2MeSH$$aHumans
000282296 650_2 $$2MeSH$$aMale
000282296 650_2 $$2MeSH$$aFemale
000282296 650_2 $$2MeSH$$aAlzheimer Disease: blood
000282296 650_2 $$2MeSH$$aAlzheimer Disease: cerebrospinal fluid
000282296 650_2 $$2MeSH$$aAged
000282296 650_2 $$2MeSH$$aBiomarkers: blood
000282296 650_2 $$2MeSH$$aLewy Body Disease: blood
000282296 650_2 $$2MeSH$$aLewy Body Disease: cerebrospinal fluid
000282296 650_2 $$2MeSH$$aCognitive Dysfunction: blood
000282296 650_2 $$2MeSH$$aCognitive Dysfunction: cerebrospinal fluid
000282296 650_2 $$2MeSH$$atau Proteins: blood
000282296 650_2 $$2MeSH$$atau Proteins: cerebrospinal fluid
000282296 650_2 $$2MeSH$$abeta-Synuclein: blood
000282296 650_2 $$2MeSH$$aAged, 80 and over
000282296 650_2 $$2MeSH$$aFrontotemporal Lobar Degeneration: blood
000282296 650_2 $$2MeSH$$aFrontotemporal Lobar Degeneration: cerebrospinal fluid
000282296 650_2 $$2MeSH$$aMiddle Aged
000282296 650_2 $$2MeSH$$aNeurofilament Proteins: blood
000282296 650_2 $$2MeSH$$aNeurofilament Proteins: cerebrospinal fluid
000282296 650_2 $$2MeSH$$aGlial Fibrillary Acidic Protein: blood
000282296 650_2 $$2MeSH$$aGlial Fibrillary Acidic Protein: cerebrospinal fluid
000282296 650_2 $$2MeSH$$aDementia: blood
000282296 650_2 $$2MeSH$$aCohort Studies
000282296 7001_ $$aBellomo, Giovanni$$b1
000282296 7001_ $$00000-0002-3819-3245$$aAlcolea, Daniel$$b2
000282296 7001_ $$aWojdala, Anna L$$b3
000282296 7001_ $$aGaetani, Lorenzo$$b4
000282296 7001_ $$00000-0002-1340-638X$$aFortea, Juan$$b5
000282296 7001_ $$00000-0003-0631-8506$$aAbu-Rumeileh, Samir$$b6
000282296 7001_ $$00000-0002-2568-5478$$aLleó, Alberto$$b7
000282296 7001_ $$00000-0001-5722-3967$$aParnetti, Lucilla$$b8
000282296 7001_ $$aBelbin, Olivia$$b9
000282296 7001_ $$00000-0003-4273-4267$$aOtto, Markus$$b10
000282296 7001_ $$0P:(DE-2719)9001560$$aOeckl, Patrick$$b11$$eLast author
000282296 773__ $$0PERI:(DE-600)1480429-3$$a10.1136/jnnp-2025-336189$$gVol. 96, no. 12, p. jnnp-2025-336189 -$$n12$$p1144 - 1153$$tJournal of neurology, neurosurgery, and psychiatry$$v96$$x0022-3050$$y2025
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