【摘要】 背景:既往研究认为阿尔茨海默病是脑灰质病变,灰质改变一直是阿尔茨海默病病理和影像研究的热点,近年来发现阿尔茨海默病进展过程中除了神经元缺失,白质的退变和脱髓鞘改变也是重要的特征,脑白质病变的研究越来越得到重视。目的:阐述阿尔茨海默病脑内存在广泛的白质损害及其发生机制,并探讨脑白质损害与认知功能的关系。方法:由第一作者检索PubMed数据库及CNKI数据库1998年1月至2019年4月的相关文献,并进行筛选、归纳和总结;英文检索词为"Alzheimer’s disease,white matter injury,neurodegeneration,oligodendrocyte",中文检索词为"阿尔茨海默病,白质损害,神经退行性变,少突胶质细胞",选择有关阿尔茨海默病、脑白质病变、少突胶质细胞死亡机制及白质改变与认知功能关系的相关研究,共检索41篇。结果与结论:阿尔茨海默病患者脑内存在广泛的白质损害,且这种改变发生较早。脑白质病变在阿尔茨海默病病理及发病机制有着重要的意义,多种途径如β-淀粉样蛋白毒性和Tau蛋白、氧化应激、兴奋性毒性作用、铁过量等都可影响少突胶质细胞,导致髓鞘的破坏。脱髓鞘或轴索损伤可以改变轴索的传导速度,直接/间接影响认知功能。可见,阿尔茨海默病白质病理改变与认知功能损害密切相关。脑白质损害与阿尔茨海默病的相关性研究不仅为阿尔茨海默病的发病机制提供理论依据,而且为阿尔茨海默病的治疗提供了新的途径。更多还原

【Abstract】 BACKGROUND: In previous studies Alzheimer’s disease was considered as a typical disease of the brain gray matter, and most attention has focused on the pathological and neuroimaging changes of gray matter in Alzheimer’s disease. Recently, in addition to neuronal loss, white matter degeneration and demyelination may be important pathophysiological features in the progress of Alzheimer’s disease. To date, much attention has been paid to the changes of white matter in Alzheimer’s disease. OBJECTIVE: To elucidate the evidence for extensive white matter abnormalities in Alzheimer’s disease and its mechanism, and to discuss the relationship between white matter changes and cognitive function. METHODS: A computer-based retrieval was performed by the first author in Pub Med and CNKI databases to search related papers published from January 1998 to April 2019 using the keywords of "Alzheimer’s disease, white matter injury, neurodegeneration, oligodendrocyte" in English and Chinese, respectively. Articles related to Alzheimer’s disease, white matter abnormalities, the mechanism of oligodendrocyte death and the relationship between white matter changes and cognitive function were selected. A total of 41 relevant literatures were retrieved. RESULTS AND CONCLUSION: White matter abnormalities widely occur in Alzheimer’s disease patients, which are probably the earliest pathological changes. White matter lesions are of important significance in the pathology and pathogenesis of Alzheimer’s disease. Several mechanisms such Aβ toxicity and tauopathy, oxidative stress, excitotoxicity, and iron overload can affect oligodendrocytes, resulting in myelin loss. Altering axonal conduction by demyelination or axonal damage can directly and/or indirectly affect cognition. In conclusion, white matter changes are closely related to cognitive impairment. Explorations on the relationship between white matter changes and the hallmark of Alzheimer’s disease cannot only provide theoretical evidence for Alzheimer’s disease pathogenesis, but also develop a new therapeutic approach for Alzheimer’s disease.更多还原