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

• Verfasst von: Halbgebauer, Steffen [VerfasserIn]
• Verfasst von: Oeckl, Patrick [VerfasserIn]
• Verfasst von: Steinacker, Petra [VerfasserIn]
• Verfasst von: Yilmazer-Hanke, Deniz [VerfasserIn]
• Verfasst von: Straub, Sarah [VerfasserIn]
• Verfasst von: Arnim, Christine von [VerfasserIn]
• Verfasst von: Frölich, Lutz [VerfasserIn]
• Verfasst von: Gomes, Luis Aragão [VerfasserIn]
• Verfasst von: Hausner, Lucrezia [VerfasserIn]
• Verfasst von: Huss, André Michael [VerfasserIn]
• Verfasst von: Jahn, Holger [VerfasserIn]
• Verfasst von: Weishaupt, Jochen H. [VerfasserIn]
• Verfasst von: Ludolph, Albert C. [VerfasserIn]
• Verfasst von: Thal, Dietmar R. [VerfasserIn]
• Verfasst von: Otto, Markus [VerfasserIn]
• Titel: Beta-synuclein in cerebrospinal fluid as an early diagnostic marker of Alzheimer’s disease
• Verf.angabe: 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
• Jahr: 2021
• Umfang: 8 S.
• Fussnoten: Published online first 30 December 2020 ; Gesehen am 07.04.2021
• Titel Quelle: Enthalten in: Journal of neurology, neurosurgery, and psychiatry
• Ort Quelle: London : BMJ Publishing Group, 1944
• Jahr Quelle: 2021
• Band/Heft Quelle: 92(2021), 4, Seite 349-356
• ISSN Quelle: 1468-330X
• DOI: doi:10.1136/jnnp-2020-324306
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1753287685

Abstract

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.