Proteomics of serum exosomes identified fibulin-1 as a novel biomarker for mild cognitive impairment

作者全名："Chen, Bo; Song, Li; Yang, Juan; Zhou, Wei-Ying; Cheng, Yuan-Yuan; Lai, Yu-Jie"

作者地址："[Chen, Bo; Zhou, Wei-Ying] Chongqing Med Univ, Coll Pharm, Chongqing, Peoples R China; [Song, Li] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Major Neurol & Mental Disorders, Dept Neurol,Chongqing Key Lab Neurol, Chongqing, Peoples R China; [Yang, Juan; Cheng, Yuan-Yuan; Lai, Yu-Jie] Chongqing Med Univ, Affiliated Hosp 3, Dept Neurol, Chongqing, Peoples R China"

通信作者："Lai, YJ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 3, Dept Neurol, Chongqing, Peoples R China."

来源：NEURAL REGENERATION RESEARCH

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000903720400036

JCR分区：Q2

影响因子：6.1

年份：2023

卷号：18

期号：3

开始页：587

结束页：593

文献类型：Article

关键词：Alzheimer's disease; biomarker; diagnosis; exosomes; fibulin; mass spectrometry; mild cognitive impairment; tandem mass tag; cell adhesion molecule; nanoparticle tracking analysis

摘要："Mild cognitive impairment (MCI) is a prodrome of Alzheimer's disease pathology. Cognitive impairment patients often have a delayed diagnosis because there are no early symptoms or conventional diagnostic methods. Exosomes play a vital role in cell-to-cell communications and can act as promising biomarkers in diagnosing diseases. This study was designed to identify serum exosomal candidate proteins that may play roles in diagnosing MCI. Mass spectrometry coupled with tandem mass tag approach-based non-targeted proteomics was used to show the differentially expressed proteins in exosomes between MCI patients and healthy controls, and these differential proteins were validated using immunoblot and enzyme-linked immunosorbent assays. Correlation of cognitive performance with the serum exosomal protein level was determined. Nanoparticle tracking analysis suggested that there was a higher serum exosome concentration and smaller exosome diameter in individuals with MCI compared with healthy controls. We identified 69 exosomal proteins that were differentially expressed between MCI patients and healthy controls using mass spectrometry analysis. Thirty-nine exosomal proteins were upregulated in MCI patients compared with those in control patients. Exosomal fibulin-1, with an area under the curve value of 0.81, may be a biomarker for an MCI diagnosis. The exosomal protein signature from MCI patients reflected the cell adhesion molecule category. In particular, higher exosomal fibulin-1 levels correlated with lower cognitive performance. Thus, this study revealed that exosomal fibulin-1 is a promising biomarker for diagnosing MCI."

基金机构：National Natural Science Foundation of China [81801071]; Top-notch Postgraduate Talent Cultivation Program of Chongqing Medical University [BJRC202106]

基金资助正文："This study was supported by the National Natural Science Foundation of China, No. 81801071 (to YJL) and Top-notch Postgraduate Talent Cultivation Program of Chongqing Medical University, No. BJRC202106 (to BC)."