Late onset Alzheimer's disease genetics implicates microglial pathways in disease risk.
Late onset Alzheimer's disease genetics implicates microglial pathways in disease risk.
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DOI：
10.1186/s13024-017-0184-x
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发表时间：
2017-05-26
影响因子：
15.1
通讯作者：
Goate AM
中科院分区：
文献类型：
--
作者：
Efthymiou AG;Goate AM
阿尔茨海默病（AD）是一种高度遗传的复杂疾病，目前尚无有效的预防或治疗方法。针对AD开发的大多数药物集中于淀粉样蛋白级联假说，该假说暗示了阿尔茨海默病斑块是该疾病的致病因素。然而，其他未充分探索的疾病相关途径可能是药物开发的更有成效的目标。基因网络分析的结果表明免疫网络富含AD;这些网络中的许多基因都属于包含常见和罕见变异的基因组区域，这些变异与AD发病风险增加相关。在这些基因中，有几个（包括CR 1，SPI 1，MS 4A，TREM 2，ABCA 7，CD 33和INPP 5D）由小胶质细胞表达，小胶质细胞是大脑的常驻免疫细胞。我们总结了基因网络和遗传学研究结果，暗示这些小胶质细胞基因参与AD，以及一些研究，这些基因在小胶质细胞和AD的背景下的表达和功能。我们认为，这些基因是有助于AD在一个非依赖性的方式。
Alzheimer’s disease (AD) is a highly heritable complex disease with no current effective prevention or treatment. The majority of drugs developed for AD focus on the amyloid cascade hypothesis, which implicates Aß plaques as a causal factor in the disease. However, it is possible that other underexplored disease-associated pathways may be more fruitful targets for drug development. Findings from gene network analyses implicate immune networks as being enriched in AD; many of the genes in these networks fall within genomic regions that contain common and rare variants that are associated with increased risk of developing AD. Of these genes, several (including CR1, SPI1, the MS4As, TREM2, ABCA7, CD33, and INPP5D) are expressed by microglia, the resident immune cells of the brain. We summarize the gene network and genetics findings that implicate that these microglial genes are involved in AD, as well as several studies that have looked at the expression and function of these genes in microglia and in the context of AD. We propose that these genes are contributing to AD in a non-Aß-dependent fashion.