趋同的基因和表达数据表明免疫与阿尔茨海默病有关。
Convergent genetic and expression data implicate immunity in Alzheimer's disease.
出版信息
Alzheimers Dement. 2015 Jun;11(6):658-71. doi: 10.1016/j.jalz.2014.05.1757. Epub 2014 Dec 20.
BACKGROUND
Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis.
METHODS
The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain.
RESULTS
ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 × 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 × 10(-11)), cholesterol transport (P = 2.96 × 10(-9)), and proteasome-ubiquitin activity (P = 1.34 × 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05).
CONCLUSIONS
The immune response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
背景
晚发性阿尔茨海默病（AD）具有遗传性，在国际阿尔茨海默病基因组计划（IGAP）中有20个基因显示出全基因组关联。为了确定该疾病背后的生物学机制，我们在通路分析中扩展了这些遗传数据。
方法
在IGAP数据中使用ALIGATOR和GSEA算法来识别相关的功能通路以及人脑中相关的基因表达网络。
结果
ALIGATOR识别出大量经过整理的生物学通路，这些通路显示出关联富集。生物学富集领域包括免疫反应（对通路进行多次检验校正后P = 3.27×10⁻¹²）、内吞作用调节（P = 1.31×10⁻¹¹）、胆固醇转运（P = 2.96×10⁻⁹）和蛋白酶体 - 泛素活性（P = 1.34×10⁻⁶）。相关基因表达分析确定了四个显著的网络模块，均与免疫反应相关（校正后P = 0.002 - 0.05）。
结论
免疫反应、内吞作用调节、胆固醇转运和蛋白质泛素化是AD治疗的主要靶点。
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