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Quantification of the trans-synaptic partners neurexin-neuroligin in CSF of neurodegenerative diseases by parallel reaction monitoring mass spectrometry

Camporesi, E; Nilsson, J; Vrillon, A; Cognat, E; Hourregue, C; Zetterberg, H; Blennow, K; ... Brinkmalm, G; + view all (2022) Quantification of the trans-synaptic partners neurexin-neuroligin in CSF of neurodegenerative diseases by parallel reaction monitoring mass spectrometry. EBioMedicine , 75 , Article 103793. 10.1016/j.ebiom.2021.103793. Green open access

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Abstract

BACKGROUND: Synaptic proteins are increasingly studied as biomarkers for synaptic dysfunction and loss, which are early and central events in Alzheimer's disease (AD) and strongly correlate with the degree of cognitive decline. In this study, we specifically investigated the synaptic binding partners neurexin (NRXN) and neuroligin (Nlgn) proteins, to assess their biomarker's potential. METHODS: we developed a parallel reaction monitoring mass spectrometric method for the simultaneous quantification of NRXNs and Nlgns in cerebrospinal fluid (CSF) of neurodegenerative diseases, focusing on AD. Specifically, NRXN-1α, NRXN-1β, NRXN-2α, NRXN-3α and Nlgn1, Nlgn2, Nlgn3 and Nlgn4 proteins were targeted. FINDINGS: The proteins were investigated in a clinical cohort including CSF from controls (n=22), mild cognitive impairment (MCI) due to AD (n=44), MCI due to other conditions (n=46), AD (n=77) and a group of non-AD dementia (n=28). No difference in levels of NRXNs and Nlgns was found between AD (both at dementia and MCI stages) or controls or the non-AD dementia group for any of the targeted proteins. NRXN and Nlgn proteins correlated strongly with each other, but only a weak correlation with the AD core biomarkers and the synaptic biomarkers neurogranin and growth-associated protein 43, was found, possibly reflecting different pathogenic processing at the synapse. INTERPRETATION: we conclude that NRXN and Nlgn proteins do not represent suitable biomarkers for synaptic pathology in AD. The panel developed here could aid in future investigations of the potential involvement of NRXNs and Nlgns in synaptic dysfunction in other disorders of the central nervous system. FUNDING: a full list of funding can be found under the acknowledgments section.

Type: Article
Title: Quantification of the trans-synaptic partners neurexin-neuroligin in CSF of neurodegenerative diseases by parallel reaction monitoring mass spectrometry
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ebiom.2021.103793
Publisher version: https://doi.org/10.1016/j.ebiom.2021.103793
Language: English
Additional information: © 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Keywords: Alzheimer's disease, biomarkers, mass spectrometry, neurexins, neuroligins, synaptic proteins
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10141687
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