Open AccessRetinal imaging demonstrates reduced capillary density in clinically unimpaired APOE ε4 gene carriers
Author(s) -
Elahi Fanny M.,
Ashimatey Senyo B.,
Bennett Daniel J.,
Walters Samantha M.,
La Joie Renaud,
Jiang Xuejuan,
Wolf Amy,
Cobigo Yann,
Staffaroni Adam M.,
Rosen Howie J.,
Miller Bruce L.,
Rabinovici Gil D.,
Kramer Joel H.,
Green Ari J.,
Kashani Amir H.
Publication year - 2021
Publication title -
alzheimer's and dementia: diagnosis, assessment and disease monitoring
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.497
H-Index - 37
ISSN - 2352-8729
DOI - 10.1002/dad2.12181
Subject(s) - apolipoprotein e , retinal , neuroscience , human brain , neuroimaging , pathology , disease , medicine , biology , psychology , ophthalmology
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.