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Targeted mass spectrometry suggests beta-synuclein as synaptic blood marker in Alzheimer’s disease

Synaptic degeneration is a major hallmark of Alzheimer’s 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...

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Main Authors: Oeckl, Patrick (Author) , Halbgebauer, Steffen (Author) , Straub, Sarah (Author) , Arnim, Christine von (Author) , Diehl-Schmid, Janine (Author) , Frölich, Lutz (Author) , Grimmer, Timo (Author) , Hausner, Lucrezia (Author) , Denk, Johannes (Author) , Jahn, Holger (Author) , Steinacker, Petra (Author) , Weishaupt, Jochen H. (Author) , Ludolph, Albert C. (Author) , Otto, Markus (Author)
Format: Article (Journal)
Language:English
Published: February 26, 2020
In: Journal of proteome research
Year: 2020, Volume: 19, Issue: 3, Pages: 1310-1318
ISSN:1535-3907
DOI:10.1021/acs.jproteome.9b00824
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1021/acs.jproteome.9b00824
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Author Notes:Patrick Oeckl, Steffen Halbgebauer, Sarah Anderl-Straub, Christine A. F. von Arnim, Janine Diehl-Schmid, Lutz Froelich, Timo Grimmer, Lucrezia Hausner, Johannes Denk, Holger Jahn, Petra Steinacker, Jochen H. Weishaupt, Albert C. Ludolph, and Markus Otto
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Summary:Synaptic degeneration is a major hallmark of Alzheimer’s 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 (βSyn) 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). βSyn 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/Parkinson’s disease dementia (n = 13), Parkinson’s 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 βSyn 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.
Item Description:Gesehen am 08.07.2021
Physical Description:Online Resource
ISSN:1535-3907
DOI:10.1021/acs.jproteome.9b00824

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