Retinal arterial Aβ40 deposition is linked with tight junction loss and cerebral amyloid angiopathy in MCI and AD patients.
Retinal arterial Aβ40 deposition is linked with tight junction loss and cerebral amyloid angiopathy in MCI and AD patients.
复制标题
视网膜动脉Aβ40 沉积与MCI 和AD 患者的紧密连接丧失和脑淀粉样血管病有关。
DOI：
10.1002/alz.13086
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发表时间：
2023
期刊：
影响因子：
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中科院分区：
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作者：
Shi,Haoshen;Koronyo,Yosef;Fuchs,Dieu-Trang;Sheyn,Julia;Jallow,Ousman;Mandalia,Krishna;Graham,StuartL;Gupta,VivekK;Mirzaei,Mehdi;Kramerov,AndreiA;Ljubimov,AlexanderV;Hawes,Debra;Miller,CarolA;Black,KeithL;Carare,RoxanaO;
目的：研究轻度认知功能障碍（MCI）和阿尔茨海默病（AD）患者视网膜血管淀粉样β蛋白（Aβ）沉积。我们检验了视网膜血管紧密连接（TJ）受损并与疾病状态相关的假设。方法在34例MCI或AD患者和27例认知正常对照的死后视网膜中测定了血管紧密连接成分和毛细血管和大血管中的Aβ表达，并与神经病理学相关。在MCI和AD患者中发现与Aβ 40大量沉积相关的claudin-5。视网膜claudin-5缺陷与脑淀粉样血管病密切相关，而ZO-1缺陷与脑病理学和认知缺陷相关。视网膜小动脉Aβ 40的大量沉积提示Aβ清除失败的常见致病机制是通过壁内动脉周围引流。
INTRODUCTIONVascular amyloid beta (Aβ) protein deposits were detected in retinas of mild cognitively impaired (MCI) and Alzheimer's disease (AD) patients. We tested the hypothesis that the retinal vascular tight junctions (TJs) were compromised and linked to disease status.METHODSTJ components and Aβ expression in capillaries and larger blood vessels were determined inpost mortemretinas from 34 MCI or AD patients and 27 cognitively normal controls and correlated with neuropathology.RESULTSSevere decreases in retinal vascular zonula occludens‐1 (ZO‐1) and claudin‐5 correlating with abundant arteriolar Aβ40deposition were identified in MCI and AD patients. Retinal claudin‐5 deficiency was closely associated with cerebral amyloid angiopathy, whereas ZO‐1 defects correlated with cerebral pathology and cognitive deficits.DISCUSSIONWe uncovered deficiencies in blood–retinal barrier markers for potential retinal imaging targets of AD screening and monitoring. Intense retinal arteriolar Aβ40deposition suggests a common pathogenic mechanism of failed Aβ clearance via intramural periarterial drainage.