关注少突胶质细胞:阿尔茨海默病治疗的新靶点

Focusing on oligodendrocytes:New targets for the treatment of Alzheimer′s disease

阿尔茨海默病(Alzheimer′s disease,AD)是一种中枢神经系统退行性疾病,起病隐匿,逐步出现记忆力减退、认知功能障碍、精神行为异常等症状。既往认为AD为皮质性痴呆,灰质有明显的病理改变。少突胶质细胞形成的髓鞘是脑白质的重要成分,然而近年来发现白质异常也是AD的重要改变,且这种改变先于Aβ聚集和Tau蛋白的发生。文章从影像学、生化和病理学角度证实AD患者存在广泛的白质损伤,这类损伤与其他病理损伤密切相关,互相影响,共同促进了AD病程的进展。多种因素如年龄、基因突变、Aβ和tau蛋白毒性、缺血性损伤等均可导致脑白质损害。对AD脑白质损伤发病机制的深入研究,将为AD的治疗提供新的靶点。

Alzheimer′s disease(AD)is a neurodegenerative disease in the central nerve system with insid⁃ious onset and progressive memory loss,cognitive decline,psychotic and behavioral changes.AD has been mainly considered as a grey matter disorder.Nevertheless,recent evidence suggests that myelin impairment may play an important role in AD pathology.It has also been found that myelin pathology may even precede Aβand tau patholo⁃gies.We summarized the evidence of white matter abnormalities from pathology and imaging studies,the role of my⁃elin in cognition and possible mechanism of myelin damage in AD.Myelin damage combined withother pathological injury contributes to the process of AD.Many factors,such as aging,gene,Aβ⁃mediated toxicity and tau,isch⁃emic injury also cause myelin breakdown.Therefore,elucidating the exact mechanisms leading to the disruption of myelin in AD may help a better understanding of AD,and thereby its prevention and treatment.