利用机器学习对脑脊液的蛋白质组分析显示了与APOE4基因型相关的独特蛋白质特征。

IF 8 1区 医学 Q1 CELL BIOLOGY
Aging Cell Pub Date : 2024-12-25 DOI:10.1111/acel.14439
Artur Shvetcov, Shannon Thomson, Ann-Na Cho, Heather M Wilkins, Joanne H Reed, Russell H Swerdlow, David A Brown, Caitlin A Finney
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引用次数: 0

摘要

与APOE4变异携带相关的蛋白质组变化与阿尔茨海默病(AD)的病理和诊断无关,目前尚不清楚。本研究调查了AD患者、轻度认知障碍患者和无认知障碍患者的APOE4蛋白质组变化。临床、APOE基因型、脑脊液(CSF)蛋白质组和AD生物标志物数据来源于阿尔茨海默病神经影像学倡议(ADNI)数据库。蛋白质组分析是使用监督机器学习完成的。我们发现了一个独立于认知诊断和AD病理生物标志物的apoe4特异性蛋白质组特征,并增加了进展为认知障碍的风险。在包括尾状和皮质在内的大脑区域以及包括内皮细胞、少突胶质细胞和星形胶质细胞在内的细胞中,蛋白质丰富。富集的外周免疫细胞包括T细胞、巨噬细胞和B细胞。APOE4携带者具有独特的脑脊液蛋白质组特征,与强大的大脑和外周免疫和炎症表型相关,这可能是APOE4携带者随着年龄增长易患认知能力下降和AD的原因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Proteome profiling of cerebrospinal fluid using machine learning shows a unique protein signature associated with APOE4 genotype.

Proteome changes associated with APOE4 variant carriage that are independent of Alzheimer's disease (AD) pathology and diagnosis are unknown. This study investigated APOE4 proteome changes in people with AD, mild cognitive impairment, and no impairment. Clinical, APOE genotype, and cerebrospinal fluid (CSF) proteome and AD biomarker data was sourced from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Proteome profiling was done using supervised machine learning. We found an APOE4-specific proteome signature that was independent of cognitive diagnosis and AD pathological biomarkers, and increased the risk of progression to cognitive impairment. Proteins were enriched in brain regions including the caudate and cortex and cells including endothelial cells, oligodendrocytes, and astrocytes. Enriched peripheral immune cells included T cells, macrophages, and B cells. APOE4 carriers have a unique CSF proteome signature associated with a strong brain and peripheral immune and inflammatory phenotype that likely underlies APOE4 carriers' vulnerability to cognitive decline and AD as they age.

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来源期刊
Aging Cell
Aging Cell Biochemistry, Genetics and Molecular Biology-Cell Biology
自引率
2.60%
发文量
212
期刊介绍: Aging Cell is an Open Access journal that focuses on the core aspects of the biology of aging, encompassing the entire spectrum of geroscience. The journal's content is dedicated to publishing research that uncovers the mechanisms behind the aging process and explores the connections between aging and various age-related diseases. This journal aims to provide a comprehensive understanding of the biological underpinnings of aging and its implications for human health. The journal is widely recognized and its content is abstracted and indexed by numerous databases and services, which facilitates its accessibility and impact in the scientific community. These include: Academic Search (EBSCO Publishing) Academic Search Alumni Edition (EBSCO Publishing) Academic Search Premier (EBSCO Publishing) Biological Science Database (ProQuest) CAS: Chemical Abstracts Service (ACS) Embase (Elsevier) InfoTrac (GALE Cengage) Ingenta Select ISI Alerting Services Journal Citation Reports/Science Edition (Clarivate Analytics) MEDLINE/PubMed (NLM) Natural Science Collection (ProQuest) PubMed Dietary Supplement Subset (NLM) Science Citation Index Expanded (Clarivate Analytics) SciTech Premium Collection (ProQuest) Web of Science (Clarivate Analytics) Being indexed in these databases ensures that the research published in Aging Cell is discoverable by researchers, clinicians, and other professionals interested in the field of aging and its associated health issues. This broad coverage helps to disseminate the journal's findings and contributes to the advancement of knowledge in geroscience.
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