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..

本研究使用的平行反应监测（Parallel Reaction Monitoring，PRM）数据采集自Q Exactive质谱仪。本次检测的靶标蛋白包括：神经素（neurexin）-1、-2、-3α，以及神经连接蛋白（neuroligin）-1、-2、-3、-4。这类蛋白均为突触黏附蛋白，可在突触间隙中相互结合，对突触的形成与功能发挥关键作用。本研究旨在探究这些蛋白作为神经退行性疾病突触生物标志物的潜力。由于这些蛋白在调控机制上紧密关联、相互交联，且神经素的扰动可能影响神经连接蛋白，反之亦然，因此本研究选择同时对所有靶标蛋白进行检测。本研究的研究对象为阿尔茨海默病（Alzheimer's Disease，AD）患者的脑脊液（Cerebrospinal Fluid，CSF）样本，队列涵盖AD患者、健康对照者、轻度认知障碍（Mild Cognitive Impairment，MCI）患者（分为AD源性MCI与其他病因MCI）以及非AD组别。既往研究表明，AD患者脑脊液中的神经素蛋白水平在轻度认知障碍阶段即已出现变化，神经连接蛋白-2亦是如此。本研究旨在复刻并拓展既往研究结果，纳入神经连接蛋白家族的其余成员，并与神经素蛋白一同开展同步检测。尽管既往研究提示这类蛋白可作为潜在生物标志物，但本研究未在任何组别中检测到蛋白水平的显著变化，因此本研究不支持将这些蛋白用作阿尔茨海默病突触功能障碍的生物标志物。本研究提出了一种可用于脑脊液样本中这些蛋白同步检测的新型靶向质谱检测方法。