Retinal imaging demonstrates reduced capillary density in clinically unimpaired APOE ε4 gene carriers

被引：22

作者：

Elahi, Fanny M. ^{[1
,2
]}

Ashimatey, Senyo B. ^{[3
]}

Bennett, Daniel J. ^{[4
]}

Walters, Samantha M. ^{[1
]}

La Joie, Renaud ^{[1
]}

Jiang, Xuejuan ^{[3
]}

Wolf, Amy ^{[1
]}

Cobigo, Yann ^{[1
]}

Staffaroni, Adam M. ^{[1
]}

Rosen, Howie J. ^{[1
]}

Miller, Bruce L. ^{[1
]}

Rabinovici, Gil D. ^{[1
,5
]}

Kramer, Joel H. ^{[1
]}

Green, Ari J. ^{[4
,6
]}

Kashani, Amir H. ^{[3
,7
]}

机构：

[1] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, Weill Inst Neurosci, San Francisco, CA 94143 USA

[2] San Francisco Vet Affairs Hlth Care Syst, San Francisco, CA USA

[3] Univ Southern Calif, Keck Sch Med, Dept Ophthalmol, USC Roski Eye Inst, Los Angeles, CA 90007 USA

[4] Univ Calif San Francisco, Dept Neurol, Div Neuroimmunol & Glial Biol, Weill Inst Neurosci, San Francisco, CA USA

[5] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA

[6] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA USA

[7] USC Ginsberg Inst Biomed Therapeut, Los Angeles, CA USA

来源：

ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING | 2021年 / 13卷 / 01期

关键词：

Alzheimer' s disease; apolipoprotein E ε 4; capillary rarefaction; preclinical biomarker; preclinical disease; vascular contributions to Alzheimer' POSITRON-EMISSION-TOMOGRAPHY; PITTSBURGH COMPOUND-B; ALZHEIMERS-DISEASE; BRAIN; DEMENTIA; HYPOPERFUSION; DEFINITION; IMPAIRMENT; OVERLAP; SYSTEM;

D O I：

10.1002/dad2.12181

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Introduction Apolipoprotein E (APOE) epsilon 4, 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 epsilon 4 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 epsilon 4 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 epsilon 4 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.

引用

页数：13

共 75 条

[1] Experimental design and the relative sensitivity of BOLD and perfusion fMRI [J].