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.
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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
Original language English
Type of outcome Article in a journal
Field of Study 30230 Other clinical medicine subjects
Country of publisher United States of America
Confidentiality degree is not subject to a state or trade secret
WWW 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
Tags Excelence Science, INT, RIV
Tags International impact, Reviewed
Changed by Changed by: Mgr. Tereza Miškechová, učo 341652. Changed: 17/5/2022 13:09.
Abstract
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.
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