Toward an Alzheimer's disease diagnosis via high-resolution blood gene expression
Toward an Alzheimer's disease diagnosis via high-resolution blood gene expression
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DOI：
10.1016/j.jalz.2009.07.001
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发表时间：
2010-01-01
影响因子：
14
通讯作者：
Bracco, Laurent
中科院分区：
文献类型：
--
作者：
Fehlbaum-Beurdeley, Pascale;Prado, Anne Charlotte Jarrige-Le;Bracco, Laurent
背景资料：有一个显着的需要可靠的分子生物标志物，以帮助在阿尔茨海默氏病（AD）的临床diagnosis.Methods：我们进行了全基因组调查的人类转录组，考虑到从80个AD患者和70个非痴呆症对照（NDC）个人的血液剪接变异的歧视权力。我们表征了由与133个基因相关的170个寡核苷酸探针组组成的血液RNA签名，其可以正确区分AD患者和NDC，灵敏度为100%，特异性为96%。在功能上，该特征突出了参与AD患者中与巨噬细胞和淋巴细胞相关的途径的基因：转化生长因子（TGF-β）信号传导、氧化应激、先天免疫和炎症、胆固醇稳态和脂筏扰动，而其他基因也可能在AD生物学中提供新的见解。这项研究提供了概念验证，即全血分析可以通过生物学相关RNA的特异性相对表达生成AD相关分类特征。这样的特征将需要通过扩展的患者队列进行验证，并进行评估以了解它是否可以将AD与其他类型的痴呆症区分开来。(C)2010年，阿尔茨海默氏症协会。All rights reserved.
Background: There is a significant need for reliable molecular biomarkers to aid in Alzheimer's disease (AD) clinical diagnosis.Methods: We performed a genome-wide investigation of the human transcriptome, taking into account the discriminatory power of splice variations from the blood of 80 AD patients and 70 nondemented control (NDC) individuals.Results: We characterized a blood RNA signature composed of 170 oligonucleotide probe sets associated with 133 genes that can correctly distinguish AD patients from NDC with a sensitivity of 100% and specificity of 96%. Functionally, this signature highlights genes involved in pathways that were associated with macrophages and lymphocytes within AD patients: Transforming growth factor (TGF-beta) signaling, oxidative stress, innate immunity and inflammation, cholesterol homeostasis, and lipid-raft perturbation, whereas other genes may also provide new insights in the biology of AD.Conclusions: This study provides proof-of-concept that whole-blood profiling can generate an AD-associated classification signature via the specific relative expression of biologically relevant RNAs. Such a signature will need to be validated with extended patient cohorts, and evaluated to learn whether it can differentiate AD from others types of dementia. (C) 2010 The Alzheimer's Association. All rights reserved.