Genetic associations of leukoaraiosis indicate pathophysiological mechanisms in white matter lesions etiology
Genetic associations of leukoaraiosis indicate pathophysiological mechanisms in white matter lesions etiology
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DOI：
10.1515/revneuro-2014-0082
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发表时间：
2015-06-01
影响因子：
4.1
通讯作者：
Tzeng, Chi-Meng
中科院分区：
文献类型：
--
作者：
Lin, Qing;Huang, Wen-Qing;Tzeng, Chi-Meng
脑白质疏松症（LA），也称为白色病变（WML）和白色高信号（WMH），是一种常见的神经影像学发现，常见于老年人的磁共振成像脑扫描，患病率为50%至100%。虽然LA无症状，但不被认为是良性的，它与许多不良临床结局相关，并增加了残疾、痴呆、抑郁、中风的风险以及总体发病率和死亡率。病理学上，LA的特征在于髓鞘和轴突的损失、斑片状脱髓鞘和WMH区域的室管膜剥脱。年龄和高血压是LA最重要的既定风险因素。然而，确切的致病机制仍不清楚。与之前的发现一起，我们最近的遗传结果强烈支持LA与免疫反应和神经炎症相关。因此，我们自信地假设LA不仅是老年人中常见的神经影像学现象，而且是中枢神经系统中新出现的神经炎症性疾病。本文从神经影像学分类、遗传学基础和推测的分子机制等方面介绍了LA的基本知识和研究现状，并提出了我们在分子遗传学研究方面的一些研究思路和成果，为进一步阐明LA的致病机制、危险因素、表观遗传指标及其在诊断和防治中的应用奠定了基础。因此，它可以为临床医生和研究人员提供一个具体的和现代的概述LA，使人们能够了解这种疾病的最新进展和未来的发展方向。
Leukoaraiosis (LA), also called white matter lesions (WMLs) and white matter hyperintensities (WMHs), is a frequent neuroimaging finding commonly seen on magnetic resonance imaging brain scans of elderly people with prevalence ranging from 50% to 100%. Although it remains asymptomatic, LA is not considered to be benign, and it is showed to be related to a host of poor clinical outcomes and increases the risk of disability, dementia, depression, stroke, and the overall morbidity and mortality. Pathologically, LA is characterized by loss of myelin and axons, patchy demyelination, and denudation of ependyma in regions of WMH. Age and hypertension are the most importantly established risk factors for LA. However, the precise pathogenic mechanisms remain unclear. Together with the previous findings, our recent genetic results strongly supported that LA is associated with immune response and neuroinflammation. Therefore, we confidently hypothesized that LA was not only a common neuroimaging phenomenon in the elderly but also an emerging neuroinflammatory disorder in the central nervous system. This article focusing on neuroimaging classification, genetics basis, and putative molecular mechanism introduced the basic knowledge and current status of LA and put forward some of our research ideas and results from our molecular genetics research, which may pave the way for deciphering the putative pathogenic mechanism, risk factor, epigenetic index, and its application in diagnostic agents or drug target for prevention and treatment. Thus, it could provide clinicians and researchers with a specific and modern overview of LA to enable the understanding of recent progress and future directions in this illness.