Journal Article

DZNE-2025-00510

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Early increase of the synaptic blood marker β-synuclein in asymptomatic autosomal dominant Alzheimer's disease.

Oeckl, P. (First author)DZNE* ; Mayer, B. ; Bateman, R. J. ; Day, G. S. ; Fox, N. C. ; Huey, E. D. ; Ibanez, L. ; Ikeuchi, T. ; Jucker, M.DZNE* ; Lee, J.-H. ; Levin, J.DZNE* ; Llibre-Guerra, J. J. ; Lopera, F. ; McDade, E. ; Morris, J. C. ; Niimi, Y. ; Roh, J. H. ; Sánchez-Valle, R. ; Schofield, P. R. ; Otto, M. ; Network, D. I. A. (Collaboration Author)

2025
Wiley Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/alz.70146

Abstract: β-synuclein is a promising blood marker to track synaptic degeneration in Alzheimer's disease (AD) but changes in preclinical AD are unclear.We investigated serum β-synuclein in 69 cognitively unimpaired mutation non-carriers, 78 cognitively unimpaired AD mutation carriers (asymptomatic AD), and 31 symptomatic mutation carriers from the Dominantly Inherited Alzheimer Network.β-synuclein levels were already higher in asymptomatic AD mutation carriers compared to non-carriers and highest in symptomatic carriers. Longitudinal trajectories and correlation analyses indicated that β-synuclein levels start to rise after amyloid deposition preceding axonal degeneration, brain atrophy and hypometabolism, and cognitive decline. β-synuclein levels were associated with cognitive impairment and gradually increased with declining cognition.Our study supports the use of blood β-synuclein to track synaptic changes in preclinical AD and as a surrogate marker for cognitive impairment which might be used in early diagnosis and to support patient selection and monitoring of treatment effects in clinical trials.Blood β-synuclein levels were already higher in asymptomatic Alzheimer's disease (AD) mutation carriers. Blood β-synuclein levels were highest in symptomatic AD mutation carriers. Blood β-synuclein levels start to rise 11 years before symptom onset. Rise of β-synuclein precedes axonal degeneration, brain atrophy, and cognitive decline. β-synuclein levels gradually increased with declining cognition.

Keyword(s): Humans (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Alzheimer Disease: blood (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Male (MeSH) ; Female (MeSH) ; Biomarkers: blood (MeSH) ; Middle Aged (MeSH) ; Mutation: genetics (MeSH) ; beta-Synuclein: blood (MeSH) ; Aged (MeSH) ; Brain: pathology (MeSH) ; Brain: diagnostic imaging (MeSH) ; Synapses (MeSH) ; Cognitive Dysfunction: blood (MeSH) ; Longitudinal Studies (MeSH) ; asymptomatic mutation carriers ; autosomal dominant Alzheimer´s disease ; blood biomarker ; preclinical Alzheimer´s disease ; synaptic degeneration ; β‐synuclein ; Biomarkers ; beta-Synuclein

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Contributing Institute(s):

1. Translational Mass Spectrometry and Biomarker Research (AG Öckl)
2. Cell Biology of Neurological Diseases (AG Jucker)
3. Clinical Neurodegeneration (AG Levin)
4. Clinical Research (Munich) (Clinical Research (Munich))

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Experiment(s):

1. Longitudinal Study on Dominantly Inherited Alzheimer's Disease

Appears in the scientific report 2025

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

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