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© 2021. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Introduction

Apolipoprotein E (APOE) ε4, the strongest non‐Mendelian genetic risk factor for Alzheimer's disease (AD), has been shown to affect brain capillaries in mice, with potential implications for AD‐related neurodegenerative disease. However, human brain capillaries cannot be directly visualized in vivo. We therefore used retinal imaging to test APOE ε4 effects on human central nervous system capillaries.

Methods

We collected retinal optical coherence tomography angiography, cognitive testing, and brain imaging in research participants and built statistical models to test genotype–phenotype associations.

Results

Our analyses demonstrate lower retinal capillary densities in early disease, in cognitively normal APOE ε4 gene carriers. Furthermore, through regression modeling with a measure of brain perfusion (arterial spin labeling), we provide support for the relevance of these findings to cerebral vasculature.

Discussion

These results suggest that APOE ε4 affects capillary health in humans and that retinal capillary measures could serve as surrogates for brain capillaries, providing an opportunity to study microangiopathic contributions to neurodegenerative disorders directly in humans.

Details

Title
Retinal imaging demonstrates reduced capillary density in clinically unimpaired APOE ε4 gene carriers
Author
Elahi, Fanny M 1 ; Ashimatey, Senyo B 2 ; Bennett, Daniel J 3 ; Walters, Samantha M 4 ; Renaud La Joie 4 ; Jiang, Xuejuan 2 ; Wolf, Amy 4 ; Cobigo, Yann 4 ; Staffaroni, Adam M 4 ; Rosen, Howie J 4 ; Miller, Bruce L 4 ; Rabinovici, Gil D 5 ; Kramer, Joel H 4 ; Green, Ari J 6 ; Kashani, Amir H 7 

 Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, San Francisco, University of California, San Francisco, California, USA; San Francisco Veterans Affairs Health Care System, San Francisco, California, USA 
 Department of Ophthalmology, USC Roski Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA 
 Department of Neurology, Division of Neuroimmunology and Glial Biology, Weill Institute for Neurosciences, San Francisco, University of California, San Francisco, California, USA 
 Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, San Francisco, University of California, San Francisco, California, USA 
 Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, San Francisco, University of California, San Francisco, California, USA; Department of Radiology and Biomedical Imaging, San Francisco, University of California, San Francisco, California, USA 
 Department of Neurology, Division of Neuroimmunology and Glial Biology, Weill Institute for Neurosciences, San Francisco, University of California, San Francisco, California, USA; Department of Ophthalmology, San Francisco, University of California, San Francisco, California, USA 
 Department of Ophthalmology, USC Roski Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA; USC Ginsberg Institute for Biomedical Therapeutics, Los Angeles, California, USA 
Section
RETINAL IMAGING
Publication year
2021
Publication date
2021
Publisher
John Wiley & Sons, Inc.
e-ISSN
23528729
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2628240404
Copyright
© 2021. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.