Defining Alzheimer’s Disease through Proteomic CSF Profiling

IF 3.8 2区生物学 Q1 BIOCHEMICAL RESEARCH METHODS

Journal of Proteome Research Pub Date : 2024-10-07 DOI:10.1021/acs.jproteome.4c0059010.1021/acs.jproteome.4c00590

Carmen Peña-Bautista, Lourdes Álvarez-Sánchez, Ángel Balaguer, Luis Raga, Lorena García-Vallés, Miguel Baquero and Consuelo Cháfer-Pericás*,

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Abstract

Alzheimer disease (AD) is the main cause of dementia, and its complexity is not yet completely understood. Proteomic profiles can provide useful information to explore the pathways involved and the heterogeneity among AD patients. A proteomic analysis was performed in cerebrospinal fluid (CSF) samples from mild cognitive impairment due to AD (MCI-AD) and control individuals; both groups were classified by amyloid β42/amyloid β40 levels in CSF (data available in BioStudies database (S-BSST1456)). The analysis based on PLS regression and volcano plot identified 7 proteins (FOLR2, PPP3CA, SMOC2, STMN1, TAGLN3, TMEM132B, and UCHL1) mainly related to protein phosphorylation, structure maintenance, inflammation, and protein degradation. Enrichment analysis revealed the involvement of different biological processes related to neuronal mechanisms and synapses, lipid and carbohydrate metabolism, immune system and inflammation, vascular, hormones, and response to stimuli, and cell signaling and adhesion. In addition, the proteomic profile showed some association with the levels of AD biomarkers in CSF. Regarding the subtypes, two MCI-AD subgroups were identified: one could be related to synapsis and neuronal functions and the other to innate immunity. The study of the proteomic profile in the CSF of AD patients reflects the heterogeneity of biochemical pathways involved in AD.

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通过脑脊液蛋白质组分析确定阿尔茨海默病

阿尔茨海默病（AD）是痴呆症的主要病因，其复杂性尚未完全明了。蛋白质组图谱可以提供有用的信息来探索阿尔茨海默病患者的发病途径和异质性。我们对轻度认知障碍所致 AD（MCI-AD）和对照组的脑脊液（CSF）样本进行了蛋白质组学分析；根据脑脊液中淀粉样β42/淀粉样β40的水平对两组进行了分类（数据可在 BioStudies 数据库（S-BSST1456）中找到）。基于 PLS 回归和火山图的分析确定了 7 个蛋白质（FOLR2、PPP3CA、SMOC2、STMN1、TAGLN3、TMEM132B 和 UCHL1），它们主要与蛋白质磷酸化、结构维持、炎症和蛋白质降解有关。富集分析表明，与神经元机制和突触、脂质和碳水化合物代谢、免疫系统和炎症、血管、激素和对刺激的反应以及细胞信号传导和粘附有关的不同生物过程都参与了其中。此外，蛋白质组图谱显示与脑脊液中的阿德生物标志物水平有一定关联。在亚型方面，发现了两个 MCI-AD 亚型：一个与突触和神经元功能有关，另一个与先天免疫有关。对AD患者脑脊液中蛋白质组概况的研究反映了AD所涉及的生化途径的异质性。

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来源期刊

Journal of Proteome Research 生物-生化研究方法

CiteScore

9.00

自引率

4.50%

发文量

251

审稿时长

3 months

期刊介绍： Journal of Proteome Research publishes content encompassing all aspects of global protein analysis and function, including the dynamic aspects of genomics, spatio-temporal proteomics, metabonomics and metabolomics, clinical and agricultural proteomics, as well as advances in methodology including bioinformatics. The theme and emphasis is on a multidisciplinary approach to the life sciences through the synergy between the different types of "omics".