Insight into white matter changes in Alzheimer’s disease: A focus on myelin and oligodendrocyte / 中国组织工程研究

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 PubMed 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.