Retinal arterial Aβ40 deposition is linked with tight junction loss and cerebral amyloid angiopathy in MCI and AD patients

Author:

Shi Haoshen1,Koronyo Yosef1,Fuchs Dieu‐Trang1,Sheyn Julia1,Jallow Ousman1,Mandalia Krishna1,Graham Stuart L.2,Gupta Vivek K.2,Mirzaei Mehdi2,Kramerov Andrei A.3,Ljubimov Alexander V.134,Hawes Debra5,Miller Carol A.5,Black Keith L.1,Carare Roxana O.6,Koronyo‐Hamaoui Maya147

Affiliation:

1. Department of Neurosurgery Maxine Dunitz Neurosurgical Research Institute Cedars‐Sinai Medical Center Los Angeles California USA

2. Macquarie Medical School Faculty of Medicine Health and Human Sciences Macquarie University Sydney New South Wales Australia

3. Department of Biomedical Sciences and Eye Program Board of Governors Regenerative Medicine Institute Cedars‐Sinai Medical Center Los Angeles California USA

4. Department of Biomedical Sciences Division of Applied Cell Biology and Physiology Cedars‐Sinai Medical Center Los Angeles California USA

5. Department of Pathology Program in Neuroscience Keck School of Medicine University of Southern California Los Angeles California USA

6. Department of Clinical Neuroanatomy University of Southampton Southampton UK

7. Department of Neurology Cedars‐Sinai Medical Center Los Angeles California USA

Abstract

AbstractINTRODUCTIONVascular 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 in post mortem retinas 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 Aβ40 deposition 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 Aβ40 deposition suggests a common pathogenic mechanism of failed Aβ clearance via intramural periarterial drainage.

Publisher

Wiley

Subject

Psychiatry and Mental health,Cellular and Molecular Neuroscience,Geriatrics and Gerontology,Neurology (clinical),Developmental Neuroscience,Health Policy,Epidemiology

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