The relationship between amyloid-beta and brain capillary endothelial cells in Alzheimer's disease  

作　　者：Yan-Li Zhang Juan Wang Zhi-Na Zhang Qiang Su Jun-Hong Guo 

机构地区：[1]Department of Neurology,First Hospital of Shanxi Medical University,Taiyuan,Shanxi Province,China [2]Department of Neurology,Sixth Hospital of Shanxi Medical University(General Hospital of Tisco),Taiyuan,Shanxi Province,China [3]School of Public Health,Shanxi Medical University,Taiyuan,Shanxi Province,China

出　　处：《Neural Regeneration Research》2022年第11期2355-2363,共9页中国神经再生研究（英文版）

基　　金：Shanxi Provincial Special Fund for the Transformation of Scientific and Technological Achievements,No.201704D13111584(to JHG)。

摘　　要：Neurovascular dysfunction,as an integral part of Alzheimer's disease,may have an important influence on the onset and progression of chronic neurodegenerative processes.The bloodbrain barrier(BBB)pathway is one of the main pathways that mediates the clearance of amyloidbeta(Aβ)in the brain parenchyma.A large number of studies have shown that receptors and ATPbinding cassette transporte rs expressed on endothelial cells play an important role in Aβtransport across the BBB,but the specific mechanism is not clear.In this review,we summarize the possible mechanisms of Aβproduction and clearance,and in particular the relationship between Aβand brain capillary endothelial cells.Aβis produced by abnormal cleavage of the amyloid precursor protein via amyloidogenic processing under pathological conditions.Dys regulation of Aβclearance is considered to be the main reason for the massive accumulation of Aβin the brain parenchyma.Several pathways mediating Aβclearance from the brain into the periphery have been identified,including the BBB pathway,the blood-cerebros pinal fluid barrier and arachnoid granule pathway,and the lymphoidrelated pathway.Brain ca pilla ry endothelial cells are the key components of Aβclearance mediated by BBB.Receptors(such as LRP1,RAGE,and FcRn)and ATP-binding cassette transporters(such as P-gp,ABCA1,and ABCC1)expressed on endothelial cells play a critical role in Aβtranscytosis across the BBB.The toxic effects of Aβcan induce dysregulation of receptor and transpo rter expression on endothelial cells.Excessive Aβexerts potent detrimental cerebrovascular effects by promoting oxidative stress,inducing chronic inflammation,and impairing endothelial structure and functions.All of these are main causes for the reduction in Aβclearance across the BBB and the accumulation of Aβin the brain parenchyma.Therefo re,studies on the intera ctions between Aβand brain capillary endothelial cells,including their receptors and transporters,studies on inhibition of the toxic effects of Aβon endothelia

关 键 词：Alzheimer's disease amyloid beta Aβclearance blood-brain barrier cerebral amyloid angiopathy DEMENTIA endothelial cells oxidative stress review THERAPEUTICS TRANSCYTOSIS 

分 类 号：R749.16[医药卫生—神经病学与精神病学]