Early increase of the synaptic blood marker β‐synuclein in asymptomatic autosomal dominant Alzheimer's disease

Oeckl, Patrick; Mayer, Benjamin; Bateman, Randall J.; Day, Gregory S.; Fox, Nick C.; Huey, Edward D.; Ibanez, Laura; Ikeuchi, Takeshi; Jucker, Mathias; Lee, Jae‐Hong; Levin, Johannes ; Llibre‐Guerra, Jorge J.; Lopera, Francisco; McDade, Eric; Morris, John C.; Niimi, Yoshiki; Roh, Jee Hoon; Sánchez‐Valle, Raquel; Schofield, Peter R. und Otto, Markus (2025): Early increase of the synaptic blood marker β‐synuclein in asymptomatic autosomal dominant Alzheimer's disease. In: Alzheimer's & Dementia, Bd. 21, Nr. 4, e70146

Abstract

Introduction: β-synuclein is a promising blood marker to track synaptic degeneration in Alzheimer's disease (AD) but changes in preclinical AD are unclear.

Methods: 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.

Results: 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.

Discussion: 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy) ; Medizin > Klinikum der LMU München > Neurologische Klinik und Poliklinik mit Friedrich-Baur-Institut
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1552-5260
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198