PDF(Pubmed)
Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: We found an APOE4-specific proteome signature that was independent of cognitive diagnosis and AD pathological biomarkers, and increased 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: We found an APOE4-specific proteome signature that was independent of cognitive diagnosis and AD pathological biomarkers, and increased 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.
CONCLUSIONS: 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.
摘要：
背景：与APOE4变异携带相关的蛋白质组变化与阿尔茨海默病（AD）病理和诊断无关，目前尚不清楚。这项研究调查了AD患者的APOE4蛋白质组变化，轻度认知障碍，也没有损害。
方法：临床，APOE基因型,脑脊液（CSF）蛋白质组和AD生物标志物数据来自阿尔茨海默病神经影像学计划（ADNI）数据库。使用监督机器学习进行蛋白质组分析。
结果：我们发现了APOE4特异性蛋白质组特征，它独立于认知诊断和AD病理生物标志物，进展为认知障碍的风险增加。蛋白质富集在脑区，包括尾状和皮质和细胞，包括内皮细胞，少突胶质细胞,和星形胶质细胞。丰富的外周免疫细胞包括T细胞，巨噬细胞，B细胞。
结论：APOE4携带者具有独特的CSF蛋白质组特征，与强烈的大脑和外周免疫和炎症表型相关，这可能是APOE4携带者对认知衰退和AD的脆弱性的基础。
方法：临床，APOE基因型,脑脊液（CSF）蛋白质组和AD生物标志物数据来自阿尔茨海默病神经影像学计划（ADNI）数据库。使用监督机器学习进行蛋白质组分析。
结果：我们发现了APOE4特异性蛋白质组特征，它独立于认知诊断和AD病理生物标志物，进展为认知障碍的风险增加。蛋白质富集在脑区，包括尾状和皮质和细胞，包括内皮细胞，少突胶质细胞,和星形胶质细胞。丰富的外周免疫细胞包括T细胞，巨噬细胞，B细胞。
结论：APOE4携带者具有独特的CSF蛋白质组特征，与强烈的大脑和外周免疫和炎症表型相关，这可能是APOE4携带者对认知衰退和AD的脆弱性的基础。
