血脑屏障破坏与阿尔茨海默病的机制研究

Blood-brain barrier destruction and the pathogenesis of Alzheimer′s disease

阿尔茨海默病(AD)是以β-淀粉样蛋白的异常沉积、神经原纤维缠结和神经元不可逆死亡为病理特征的多因素和异质性神经退行性疾病。AD的病因及发病机制至今仍不清楚。近年来的研究发现血脑屏障损害与AD发病密切相关,血脑屏障完整性的破坏被认为是AD的早期生物标志物。AD病理与血脑屏障损伤相互作用,形成恶性循环,促进AD进展,而AD的主要风险基因载脂蛋白E也参与血脑屏障完整性的调控。通过脑脊液和动态对比增强磁共振成像的在体评估可发现血脑屏障完整性的改变。文中简述了近年来AD中血脑屏障破坏的机制研究和检测方法的进展,并探讨未来的研究方向。

Alzheimer′s disease(AD)is a multifactorial and heterogeneous neurodegenerative disease,which is characterized by the abnormal amyloid-βdeposition,neurofibrillary tangles,and irreversible death of progressive neuron.To date,the etiology and pathogenesis of AD are far from clear.Recent studies have suggested that the destruction of the blood brain barrier(BBB)integrity was closely associated with the pathogenesis of AD,and the destructed BBB integrity appeared to be early manifestation of AD pathological markers.Numerous evidences indicate that there is an interaction between BBB destruction and AD pathological markers,leading to a vicious cycle and promoting AD progression.Besides,apolipoprotein E,as the main risk gene of AD,is also involved in the regulation of BBB integrity.Disrupted integrity of BBB can be detected through cerebrospinal fluid test and neuroimaging(such as dynamic contrast-enhanced magnetic resonance imaging)in vivo.This review briefly describes the advancement of the underlying mechanism and detection methods of BBB destruction on AD pathophysiology in recent years.