RT Journal Article
SR Electronic
T1 Beta-synuclein in cerebrospinal fluid as an early diagnostic marker of Alzheimer’s disease
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 349
OP 356
DO 10.1136/jnnp-2020-324306
VO 92
IS 4
A1 Steffen Halbgebauer
A1 Patrick Oeckl
A1 Petra Steinacker
A1 Deniz Yilmazer-Hanke
A1 Sarah Anderl-Straub
A1 Christine von Arnim
A1 Lutz Froelich
A1 Luis Aragão Gomes
A1 Lucrezia Hausner
A1 Andre Huss
A1 Holger Jahn
A1 Jochen Weishaupt
A1 Albert C Ludolph
A1 Dietmar R Thal
A1 Markus Otto
YR 2021
UL http://jnnp.bmj.com/content/92/4/349.abstract
AB 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.