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C1q 在阿尔茨海默病患者脑脊液来源的细胞外囊泡中增加：一项多队列蛋白质组学和免疫测定验证研究。

C1q is increased in cerebrospinal fluid-derived extracellular vesicles in Alzheimer's disease: A multi-cohort proteomics and immuno-assay validation study.

机构信息

German Center for Neurodegenerative Diseases, DZNE, Bonn, Germany.

Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen, Germany.

出版信息

Alzheimers Dement. 2023 Nov;19(11):4828-4840. doi: 10.1002/alz.13066. Epub 2023 Apr 6.

DOI:10.1002/alz.13066

PMID:37023079

Abstract

INTRODUCTION

Extracellular vesicles (EVs) may propagate and modulate Alzheimer's disease (AD) pathology. We aimed to comprehensively characterize the proteome of cerebrospinal fluid (CSF) EVs to identify proteins and pathways altered in AD.

METHODS

CSF EVs were isolated by ultracentrifugation (Cohort 1) or Vn96 peptide (Cohort 2) from non-neurodegenerative controls (n = 15, 16) and AD patients (n = 22, 20, respectively). EVs were subjected to untargeted quantitative mass spectrometry-based proteomics. Results were validated by enzyme-linked immunosorbent assay (ELISA) in Cohorts 3 and 4, consisting of controls (n = 16, n = 43, (Cohort3, Cohort4)), and patients with AD (n = 24, n = 100).

RESULTS

We found > 30 differentially expressed proteins in AD CSF EVs involved in immune-regulation. Increase of C1q levels in AD compared to non-demented controls was validated by ELISA (∼ 1.5 fold, p (Cohort 3) = 0.03, p (Cohort 4) = 0.005).

DISCUSSION

EVs may be utilized as a potential biomarker and may play a so far unprecedented role in immune-regulation in AD.

摘要

简介

细胞外囊泡 (EVs) 可能会传播并调节阿尔茨海默病 (AD) 病理。我们旨在全面描述脑脊液 (CSF) EVs 的蛋白质组，以确定 AD 中改变的蛋白质和途径。

方法

通过超速离心（队列 1）或 Vn96 肽（队列 2）从非神经退行性对照组（n = 15，16）和 AD 患者（n = 22，20）中分离 CSF EVs。EVs 进行非靶向定量基于质谱的蛋白质组学分析。结果通过酶联免疫吸附测定法 (ELISA) 在队列 3 和 4 中进行验证，队列 3 和 4 包括对照组 (n = 16，n = 43) 和 AD 患者 (n = 24，n = 100)。