Journal Article

DZNE-2026-00998

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Changes in serum β-synuclein precede blood biomarkers of Alzheimer pathology in Down syndrome.

Cervantes González, A. ; Morcillo-Nieto, A. O. ; Serrano, S. ; Benejam, B. ; Videla, L. ; Barroeta, I. ; Fernández, S. ; Del Hoyo Soriano, L. ; Hernandez, A. S. ; Maure-Blesa, L. ; Vaqué-Alcázar, L. ; Arranz, J. ; Rodríguez-Baz, Í. ; Aranha, M. R. ; Perlaza, D. ; Lidón, L. ; Alcolea, D. ; Bejanin, A. ; Carmona-Iragui, M. ; Fortea, J. ; Lleó, A. ; Otto, M. ; Oeckl, P. (Last author)DZNE* ; Belbin, O.

2026
Wiley Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/alz.71860

Abstract: There is a need for early, objective markers of Alzheimer's disease (AD)-related synapse dysfunction in adults with Down syndrome (DS). The presynaptic protein β-synuclein is elevated in the blood of adults with DS. This study evaluates the positioning of these changes relative to changes in pathophysiological blood biomarkers along the AD continuum.We quantified serum β-synuclein using immunoprecipitation-mass spectrometry in a cross-sectional cohort (n = 131) spanning the AD continuum in adults with DS (n = 88) and cognitively unimpaired euploid controls (n = 43).β-synuclein levels were elevated in individuals with DS (p < 0.001), preceding symptom onset by two decades and changes in other blood biomarkers (tau phosphorylated at threonine 217, neurofilament light, glial fibrillary acidic protein) by several years. Higher β-synuclein was associated with cortical atrophy (p < 0.001) and hypometabolism (p < 0.001) in AD-vulnerable regions and reduced episodic memory (p < 0.009).These findings consolidate β-synuclein as an early blood-based biomarker of synaptic dysfunction and provide insight into early AD-related mechanisms.

Keyword(s): Humans (MeSH) ; Down Syndrome: blood (MeSH) ; Down Syndrome: complications (MeSH) ; Down Syndrome: pathology (MeSH) ; Female (MeSH) ; Alzheimer Disease: blood (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Alzheimer Disease: complications (MeSH) ; Biomarkers: blood (MeSH) ; Male (MeSH) ; beta-Synuclein: blood (MeSH) ; Cross-Sectional Studies (MeSH) ; Middle Aged (MeSH) ; Adult (MeSH) ; tau Proteins: blood (MeSH) ; Neurofilament Proteins: blood (MeSH) ; Glial Fibrillary Acidic Protein: blood (MeSH) ; Aged (MeSH) ; Brain: pathology (MeSH) ; Alzheimer's disease ; Down syndrome ; beta‐synuclein ; blood biomarkers ; Biomarkers ; beta-Synuclein ; tau Proteins ; Neurofilament Proteins ; Glial Fibrillary Acidic Protein

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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)

Appears in the scientific report 2026

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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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