Neurexin-neuroligin MS panel

Parallel reaction monitoring (PRM) data acquired on a Q Exactive mass spectrometer. Targeted proteins: neurexin-1, -2, -3 alpha, neuroligin -1, -2, -3, -4. These are synaptic adhesion proteins, binding to each other at the synaptic cleft and important for synapse formation and function. In this study we aimed at investigating their potential as synaptic biomarkers for neurodegenerative diseases. These proteins are tightly related and interconnected in their regulatory mechanisms, therefore we aimed at investigating them simultaneously, as perturbation of neurexins could affect neuroligins and vice versa. The focus of the study was on Alzheimer's disease (AD) and cerebrospinal fluid (CSF) samples from a cohort including AD, control, mild cognitive impairment (MCI) cases (due to AD and due to other causes) and non-AD group was investigated. Previous studies showed changing levels of neurexins proteins in CSF of AD patients, already at the MCI stage, and also for neuroligin-2. In this study we wanted to reproduce and expand previous results also including the other members of the neuroligin family and investigate them simultaneously with the neurexin proteins. Despite previous studies suggesting these proteins as possible biomarkers, in our investigation the protein levels did not change in any of the groups, therefore we do not support the use of these proteins as biomarkers for synaptic dysfunction in AD. We here present a novel targeted mass spectrometry method for their simultaneous investigation in CSF samples..