%0 Journal Article
%A Oeckl, Patrick
%A Mayer, Benjamin
%A Bateman, Randall J
%A Day, Gregory S
%A Fox, Nick C
%A Huey, Edward D
%A Ibanez, Laura
%A Ikeuchi, Takeshi
%A Jucker, Mathias
%A Lee, Jae-Hong
%A Levin, Johannes
%A Llibre-Guerra, Jorge J
%A Lopera, Francisco
%A McDade, Eric
%A Morris, John C
%A Niimi, Yoshiki
%A Roh, Jee Hoon
%A Sánchez-Valle, Raquel
%A Schofield, Peter R
%A Otto, Markus
%T Early increase of the synaptic blood marker β-synuclein in asymptomatic autosomal dominant Alzheimer's disease.
%J Alzheimer's and dementia
%V 21
%N 4
%@ 1552-5260
%C Hoboken, NJ
%I Wiley
%M DZNE-2025-00510
%P e70146
%D 2025
%X 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.
%K Humans
%K Alzheimer Disease: genetics
%K Alzheimer Disease: blood
%K Alzheimer Disease: pathology
%K Male
%K Female
%K Biomarkers: blood
%K Middle Aged
%K Mutation: genetics
%K beta-Synuclein: blood
%K Aged
%K Brain: pathology
%K Brain: diagnostic imaging
%K Synapses
%K Cognitive Dysfunction: blood
%K Longitudinal Studies
%K asymptomatic mutation carriers (Other)
%K autosomal dominant Alzheimer´s disease (Other)
%K blood biomarker (Other)
%K preclinical Alzheimer´s disease (Other)
%K synaptic degeneration (Other)
%K β‐synuclein (Other)
%K Biomarkers (NLM Chemicals)
%K beta-Synuclein (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40207431
%R 10.1002/alz.70146
%U https://pub.dzne.de/record/277978