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We tested the hypothesis that the retinal vascular tight junctions (TJs) were compromised and linked to disease status.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>TJ components and A\u03b2 expression in capillaries and larger blood vessels were determined in <jats:italic>post mortem<\/jats:italic> retinas from 34 MCI or AD patients and 27 cognitively normal controls and correlated with neuropathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Severe decreases in retinal vascular zonula occludens\u20101 (ZO\u20101) and claudin\u20105 correlating with abundant arteriolar A\u03b2<jats:sub>40<\/jats:sub> deposition were identified in MCI and AD patients. Retinal claudin\u20105 deficiency was closely associated with cerebral amyloid angiopathy, whereas ZO\u20101 defects correlated with cerebral pathology and cognitive deficits.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>We uncovered deficiencies in blood\u2013retinal barrier markers for potential retinal imaging targets of AD screening and monitoring. Intense retinal arteriolar A\u03b2<jats:sub>40<\/jats:sub> deposition suggests a common pathogenic mechanism of failed A\u03b2 clearance via intramural periarterial drainage.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.13086","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T07:04:04Z","timestamp":1683788644000},"page":"5185-5197","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Retinal arterial A\u03b2<sub>40<\/sub> deposition is linked with tight junction loss and cerebral amyloid angiopathy in MCI and AD patients"],"prefix":"10.1002","volume":"19","author":[{"given":"Haoshen","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Maxine Dunitz Neurosurgical Research Institute Cedars\u2010Sinai Medical Center  Los Angeles California 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