Targeted Mass Spectrometry Suggests Beta-Synuclein as Synaptic
Blood Marker in Alzheimer's Disease

J 2020

Targeted Mass Spectrometry Suggests Beta-Synuclein as Synaptic Blood Marker in Alzheimer's Disease

OECKL, P., S. HALBGEBAUER, S. ANDERL-STRAUB, CAF. VON ARNIM, J. DIEHL-SCHMID et. al.

Basic information

Original name

Targeted Mass Spectrometry Suggests Beta-Synuclein as Synaptic Blood Marker in Alzheimer's Disease

Authors

OECKL, P. (guarantor), S. HALBGEBAUER, S. ANDERL-STRAUB, CAF. VON ARNIM, J. DIEHL-SCHMID, L. FROELICH, T. GRIMMER, L. HAUSNER, J. DENK, H. JAHN, P. STEINACKER, JH. WEISHAUPT, AC. LUDOLPH and M. OTTO

Edition

Journal of Proteome Research, Washington, USA, AMER CHEMICAL SOC, 2020, 1535-3893

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30230 Other clinical medicine subjects

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

FAIRPARK II

Impact factor

Impact factor: 4.466

RIV identification code

RIV/00216224:14110/20:00124113

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1021/acs.jproteome.9b00824

UT WoS

000518876700029

Keywords (in Czech)

Alzheimer's disease; beta-synuclein; Creutzfeldt-Jakob disease; mass spectrometry; synaptic blood biomarker; MRM; cerebrospinal fluid; dementia

Keywords in English

Alzheimer's disease; beta-synuclein; Creutzfeldt-Jakob disease; mass spectrometry; synaptic blood biomarker; MRM; cerebrospinal fluid; dementia

Abstract

V originále

Synaptic degeneration is a major hallmark of Alzheimers disease (AD) and the best pathological correlate of cognitive dysfunction. Synaptic markers are therefore a highly desired read-out for patient diagnosis and possible follow-up in clinical trials. Several synaptic markers for AD are described in cerebrospinal fluid (CSF), but studies in blood have failed so far. Using quantitative mass spectrometry (IP-MS, MRM) we observed increased concentrations of the presynaptic protein beta-synuclein (beta Syn) in CSF and blood of AD patients (n = 64, p < 0.01) and confirmed this finding in two validation cohorts (AD: n = 40 and n = 49, controls: n = 44 and n = 25). beta Syn was already increased in patients with mild cognitive impairment (p < 0.01) and was also markedly increased in Creutzfeldt-Jakob disease (CJD; n = 25, p < 0.001) but not behavioral variant frontotemporal dementia (n = 16), dementia with Lewy bodies/Parkinsons disease dementia (n = 13), Parkinsons disease (n = 25), or amyotrophic lateral sclerosis (n = 30). The diagnostic sensitivity and specificity for CJD versus other neurodegenerative diseases was >= 96%. These findings suggest beta Syn as a candidate blood marker for synaptic degeneration that might be used in clinical AD trials and patient follow-up as part of the recently suggested ATN biomarker panel. It can also serve in the differential diagnosis of CJD.

Links

90128, large research infrastructures

Name: CZECRIN III

Citovat

OECKL, P., S. HALBGEBAUER, S. ANDERL-STRAUB, CAF. VON ARNIM, J. DIEHL-SCHMID, L. FROELICH, T. GRIMMER, L. HAUSNER, J. DENK, H. JAHN, P. STEINACKER, JH. WEISHAUPT, AC. LUDOLPH and M. OTTO. Targeted Mass Spectrometry Suggests Beta-Synuclein as Synaptic Blood Marker in Alzheimer's Disease. Journal of Proteome Research. Washington, USA: AMER CHEMICAL SOC, 2020, vol. 19, No 3, p. 1310-1318. ISSN 1535-3893. Available from: https://dx.doi.org/10.1021/acs.jproteome.9b00824.

@article{1833139,
   author = {Oeckl, P. and Halbgebauer, S. and AnderlandStraub, S. and von Arnim, CAF. and DiehlandSchmid, J. and Froelich, L. and Grimmer, T. and Hausner, L. and Denk, J. and Jahn, H. and Steinacker, P. and Weishaupt, JH. and Ludolph, AC. and Otto, M.},
   article_location = {Washington, USA},
   article_number = {3},
   doi = {http://dx.doi.org/10.1021/acs.jproteome.9b00824},
   keywords = {Alzheimer's disease; beta-synuclein; Creutzfeldt-Jakob disease; mass spectrometry; synaptic blood biomarker; MRM; cerebrospinal fluid; dementia},
   language = {eng},
   issn = {1535-3893},
   journal = {Journal of Proteome Research},
   note = {FairPark II},
   title = {Targeted Mass Spectrometry Suggests Beta-Synuclein as Synaptic Blood Marker in Alzheimer's Disease},
   url = {https://pubs.acs.org/doi/10.1021/acs.jproteome.9b00824},
   volume = {19},
   year = {2020}
}

TY  - JOUR
ID  - 1833139
AU  - Oeckl, P. - Halbgebauer, S. - Anderl-Straub, S. - von Arnim, CAF. - Diehl-Schmid, J. - Froelich, L. - Grimmer, T. - Hausner, L. - Denk, J. - Jahn, H. - Steinacker, P. - Weishaupt, JH. - Ludolph, AC. - Otto, M.
PY  - 2020
TI  - Targeted Mass Spectrometry Suggests Beta-Synuclein as Synaptic Blood Marker in Alzheimer's Disease
JF  - Journal of Proteome Research
VL  - 19
IS  - 3
SP  - 1310-1318
EP  - 1310-1318
PB  - AMER CHEMICAL SOC
SN  - 15353893
N1  - FairPark II
KW  - Alzheimer's disease
KW  - beta-synuclein
KW  - Creutzfeldt-Jakob disease
KW  - mass spectrometry
KW  - synaptic blood biomarker
KW  - MRM
KW  - cerebrospinal fluid
KW  - dementia
UR  - https://pubs.acs.org/doi/10.1021/acs.jproteome.9b00824
N2  - Synaptic degeneration is a major hallmark of Alzheimers disease (AD) and the best pathological correlate of cognitive dysfunction. Synaptic markers are therefore a highly desired read-out for patient diagnosis and possible follow-up in clinical trials. Several synaptic markers for AD are described in cerebrospinal fluid (CSF), but studies in blood have failed so far. Using quantitative mass spectrometry (IP-MS, MRM) we observed increased concentrations of the presynaptic protein beta-synuclein (beta Syn) in CSF and blood of AD patients (n = 64, p < 0.01) and confirmed this finding in two validation cohorts (AD: n = 40 and n = 49, controls: n = 44 and n = 25). beta Syn was already increased in patients with mild cognitive impairment (p < 0.01) and was also markedly increased in Creutzfeldt-Jakob disease (CJD; n = 25, p < 0.001) but not behavioral variant frontotemporal dementia (n = 16), dementia with Lewy bodies/Parkinsons disease dementia (n = 13), Parkinsons disease (n = 25), or amyotrophic lateral sclerosis (n = 30). The diagnostic sensitivity and specificity for CJD versus other neurodegenerative diseases was >= 96%. These findings suggest beta Syn as a candidate blood marker for synaptic degeneration that might be used in clinical AD trials and patient follow-up as part of the recently suggested ATN biomarker panel. It can also serve in the differential diagnosis of CJD.
ER  -

OECKL, P., S. HALBGEBAUER, S. ANDERL-STRAUB, CAF. VON ARNIM, J. DIEHL-SCHMID, L. FROELICH, T. GRIMMER, L. HAUSNER, J. DENK, H. JAHN, P. STEINACKER, JH. WEISHAUPT, AC. LUDOLPH and M. OTTO. Targeted Mass Spectrometry Suggests Beta-Synuclein as Synaptic Blood Marker in Alzheimer's Disease. \textit{Journal of Proteome Research}. Washington, USA: AMER CHEMICAL SOC, 2020, vol.~19, No~3, p.~1310-1318. ISSN~1535-3893. Available from: https://dx.doi.org/10.1021/acs.jproteome.9b00824.

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