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

• Verfasst von: Oeckl, Patrick [VerfasserIn]
• Verfasst von: Halbgebauer, Steffen [VerfasserIn]
• Verfasst von: Straub, Sarah [VerfasserIn]
• Verfasst von: Arnim, Christine von [VerfasserIn]
• Verfasst von: Diehl-Schmid, Janine [VerfasserIn]
• Verfasst von: Frölich, Lutz [VerfasserIn]
• Verfasst von: Grimmer, Timo [VerfasserIn]
• Verfasst von: Hausner, Lucrezia [VerfasserIn]
• Verfasst von: Denk, Johannes [VerfasserIn]
• Verfasst von: Jahn, Holger [VerfasserIn]
• Verfasst von: Steinacker, Petra [VerfasserIn]
• Verfasst von: Weishaupt, Jochen H. [VerfasserIn]
• Verfasst von: Ludolph, Albert C. [VerfasserIn]
• Verfasst von: Otto, Markus [VerfasserIn]
• Titel: Targeted mass spectrometry suggests beta-synuclein as synaptic blood marker in Alzheimer’s disease
• Verf.angabe: 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
• E-Jahr: 2020
• Jahr: February 26, 2020
• Umfang: 9 S.
• Fussnoten: Gesehen am 08.07.2021
• Titel Quelle: Enthalten in: Journal of proteome research
• Ort Quelle: Washington, DC : ACS Publications, 2002
• Jahr Quelle: 2020
• Band/Heft Quelle: 19(2020), 3, Seite 1310-1318
• ISSN Quelle: 1535-3907
• DOI: doi:10.1021/acs.jproteome.9b00824
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1762501740

Abstract

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.