Alteration of Vascular Endothelial Cadherin in Alzheimer's Disease Patient and Mouse Model

Title
Alteration of Vascular Endothelial Cadherin in Alzheimer's Disease Patient and Mouse Model
Authors
류훈조선정임현정석지웅이대훈조철만조상미박문호한창수Neil KowallRudolph E. Tanzi고영호
Issue Date
2018-09
Publisher
biorxiv
Citation
VOL 게재예정, 게재예정
Abstract
Alzheimer's disease (AD) is characterized by amyloid plaques and pathologic cerebrovascular remodeling. Cerebrovascular abnormalities may contribute to the pathology of AD, but the molecular mechanisms are not fully understood. In this study, we evaluated blood-brain barrier (BBB) disruption and the role of VE-cadherin in the progression of amyloid pathology. Here, we determined that levels of VE-cadherin are decreased in brain vessels of AD patients and mouse model of AD. In vitro experiments showed that the disappearance of VE-cadherin by beta-amyloid at the endothelial cell surface was due to cleavage of VE-cadherin. The disappearance of VE-cadherin in brain vessels was also seen in amyloid precursor protein transgenic mice. In the postmortem brain of individuals with AD, furthermore, levels of VE-cadherin were significantly reduced in vessels. Dementia patients showed a distinct blood biochemical profile characterized by high soluble VE-cadherin (sVEC). There was a strong association between plasma sVEC (adjusted odds ratio = 3.41, P < 0.001) and dementia. These results suggest that measurements of plasma VE-cadherin could have the potential for predicting the risk of progressive AD.
URI
http://pubs.kist.re.kr/handle/201004/68916
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