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Halbgebauer, Steffen; Oeckl, Patrick; Steinacker, Petra; Yilmazer-Hanke, Deniz; Anderl-Straub, Sarah; von Arnim, Christine; Froelich, Lutz; Gomes, Luis Aragão; Hausner, Lucrezia; Huss, Andre; Jahn, Holger; Weishaupt, Jochen; Ludolph, Albert C; Thal, Dietmar R; Otto, Markus

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

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  • Media type: E-Article
  • Title: Beta-synuclein in cerebrospinal fluid as an early diagnostic marker of Alzheimer’s disease
  • Contributor: Halbgebauer, Steffen; Oeckl, Patrick; Steinacker, Petra; Yilmazer-Hanke, Deniz; Anderl-Straub, Sarah; von Arnim, Christine; Froelich, Lutz; Gomes, Luis Aragão; Hausner, Lucrezia; Huss, Andre; Jahn, Holger; Weishaupt, Jochen; Ludolph, Albert C; Thal, Dietmar R; Otto, Markus
  • Published: BMJ, 2021
  • Published in: Journal of Neurology, Neurosurgery & Psychiatry, 92 (2021) 4, Seite 349-356
  • Language: English
  • DOI: 10.1136/jnnp-2020-324306
  • ISSN: 0022-3050; 1468-330X
  • Origination:
  • Footnote:
  • Description: ObjectiveSynaptic 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.MethodsWe 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.ResultsBeta-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).ConclusionWe 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.