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

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Beta-synuclein in cerebrospinal fluid as an early diagnostic marker of Alzheimer's disease. / 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.

In: J NEUROL NEUROSUR PS, Vol. 92, No. 4, 04.2021, p. 349-356.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Halbgebauer, S, Oeckl, P, Steinacker, P, Yilmazer-Hanke, D, Anderl-Straub, S, von Arnim, C, Froelich, L, Gomes, LA, Hausner, L, Huss, A, Jahn, H, Weishaupt, J, Ludolph, AC, Thal, DR & Otto, M 2021, 'Beta-synuclein in cerebrospinal fluid as an early diagnostic marker of Alzheimer's disease', J NEUROL NEUROSUR PS, vol. 92, no. 4, pp. 349-356. https://doi.org/10.1136/jnnp-2020-324306

APA

Halbgebauer, S., Oeckl, P., Steinacker, P., Yilmazer-Hanke, D., Anderl-Straub, S., von Arnim, C., Froelich, L., Gomes, L. A., Hausner, L., Huss, A., Jahn, H., Weishaupt, J., Ludolph, A. C., Thal, D. R., & Otto, M. (2021). Beta-synuclein in cerebrospinal fluid as an early diagnostic marker of Alzheimer's disease. J NEUROL NEUROSUR PS, 92(4), 349-356. https://doi.org/10.1136/jnnp-2020-324306

Vancouver

Halbgebauer S, Oeckl P, Steinacker P, Yilmazer-Hanke D, Anderl-Straub S, von Arnim C et al. Beta-synuclein in cerebrospinal fluid as an early diagnostic marker of Alzheimer's disease. J NEUROL NEUROSUR PS. 2021 Apr;92(4):349-356. https://doi.org/10.1136/jnnp-2020-324306

Bibtex

@article{3d5cd3cf0036437fb8e6b4374f91af3a,
title = "Beta-synuclein in cerebrospinal fluid as an early diagnostic marker of Alzheimer's disease",
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.",
author = "Steffen Halbgebauer and Patrick Oeckl and Petra Steinacker and Deniz Yilmazer-Hanke and Sarah Anderl-Straub and {von Arnim}, Christine and Lutz Froelich and Gomes, {Luis Arag{\~a}o} and Lucrezia Hausner and Andre Huss and Holger Jahn and Jochen Weishaupt and Ludolph, {Albert C} and Thal, {Dietmar R} and Markus Otto",
note = "{\textcopyright} Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.",
year = "2021",
month = apr,
doi = "10.1136/jnnp-2020-324306",
language = "English",
volume = "92",
pages = "349--356",
journal = "J NEUROL NEUROSUR PS",
issn = "0022-3050",
publisher = "BMJ PUBLISHING GROUP",
number = "4",

}

RIS

TY - JOUR

T1 - Beta-synuclein in cerebrospinal fluid as an early diagnostic marker of Alzheimer's disease

AU - Halbgebauer, Steffen

AU - Oeckl, Patrick

AU - Steinacker, Petra

AU - Yilmazer-Hanke, Deniz

AU - Anderl-Straub, Sarah

AU - von Arnim, Christine

AU - Froelich, Lutz

AU - Gomes, Luis Aragão

AU - Hausner, Lucrezia

AU - Huss, Andre

AU - Jahn, Holger

AU - Weishaupt, Jochen

AU - Ludolph, Albert C

AU - Thal, Dietmar R

AU - Otto, Markus

N1 - © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2021/4

Y1 - 2021/4

N2 - 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.

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.

U2 - 10.1136/jnnp-2020-324306

DO - 10.1136/jnnp-2020-324306

M3 - SCORING: Journal article

C2 - 33380492

VL - 92

SP - 349

EP - 356

JO - J NEUROL NEUROSUR PS

JF - J NEUROL NEUROSUR PS

SN - 0022-3050

IS - 4

ER -