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Beta-synuclein in cerebrospinal fluid as an early diagnostic marker of Alzheimer’s disease

Objective Synaptic loss plays a major role in Alzheimer’s disease (AD). However so far no neurochemical marker for synaptic loss has been introduced into clinical routine. By mass spectrometry beta-synuclein was established as a candidate marker. We now aimed to set up a novel ELISA for beta-synucle...

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Main Authors: Halbgebauer, Steffen (Author) , Oeckl, Patrick (Author) , Steinacker, Petra (Author) , Yilmazer-Hanke, Deniz (Author) , Straub, Sarah (Author) , Arnim, Christine von (Author) , Frölich, Lutz (Author) , Gomes, Luis Aragão (Author) , Hausner, Lucrezia (Author) , Huss, André Michael (Author) , Jahn, Holger (Author) , Weishaupt, Jochen H. (Author) , Ludolph, Albert C. (Author) , Thal, Dietmar R. (Author) , Otto, Markus (Author)
Format: Article (Journal)
Language:English
Published: 2021
In: Journal of neurology, neurosurgery, and psychiatry
Year: 2021, Volume: 92, Issue: 4, Pages: 349-356
ISSN:1468-330X
DOI:10.1136/jnnp-2020-324306
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1136/jnnp-2020-324306
Verlag, lizenzpflichtig, Volltext: https://jnnp.bmj.com/content/92/4/349
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Author Notes:Steffen Halbgebauer, Patrick Oeckl, Petra Steinacker, Deniz Yilmazer-Hanke, Sarah Anderl-Straub, Christine von Arnim, Lutz Froelich, Luis Aragão Gomes, Lucrezia Hausner, Andre Huss, Holger Jahn, Jochen Weishaupt, Albert C Ludolph, Dietmar R Thal, Markus Otto
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Summary:Objective Synaptic loss plays a major role in Alzheimer’s disease (AD). However so far no neurochemical marker for synaptic loss has been introduced into clinical routine. By mass spectrometry beta-synuclein was established as a candidate marker. We now aimed to set up a novel ELISA for beta-synuclein for evaluation of its potential as a diagnostic and predictive marker for AD. - Methods We analysed in total 393 patients from four specialised centres. The diagnostic groups comprised: AD (n=151), behavioural variant frontotemporal dementia (bvFTD, n=18), Parkinson syndrome (n=46), Creutzfeldt-Jakob disease (CJD, n=23), amyotrophic lateral sclerosis (ALS, n=29), disease control (n=66) and 60 non-neurodegenerative control patients. Results were compared with core AD biomarkers (total tau, phospho-tau and amyloid-β peptide 1-42). Additionally, coexistence of beta-synuclein with vesicular glutamate transporter 1 (VGLUT1) was determined and beta-synuclein levels were quantified in brain homogenates. - Results Beta-synuclein levels quantified with the newly established ELISA correlated strongly with antibody-free quantitative mass spectrometry data (r=0.92 (95% CI: 0.89 to 0.94), p<0.0001). Cerebrospinal fluid (CSF) beta-synuclein levels were increased in AD-mild cognitive impairment (p<0.0001), AD dementia (p<0.0001) and CJD (p<0.0001), but not in bvFTD, Parkinson syndrome or ALS. Furthermore, beta-synuclein was localised in VGLUT1-positive glutamatergic synapses, and its expression was significantly reduced in brain tissue from patients with AD (p<0.01). - Conclusion We successfully established a sensitive and robust ELISA for the measurement of brain-enriched beta-synuclein, which we could show is localised in glutamatergic synapses. We confirmed previous, mass spectrometry-based observations of increased beta-synuclein levels in CSF of patients with AD and CJD supporting its potential use as a marker of synaptic degeneration.
Item Description:Published online first 30 December 2020
Gesehen am 07.04.2021
Physical Description:Online Resource
ISSN:1468-330X
DOI:10.1136/jnnp-2020-324306

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