Exploratory Analysis of APOE ε4-Stratified Associations Between Plasma Alzheimer's Biomarkers and Retinal Imaging Metrics in Cognitively Normal Adults.
Alex Choi, Alice Haystead, Rachel D'Cunha, John Hsu, Michael Zhu, Kim G Johnson, Michael W Lutz, Heather Whitson, Dilraj S Grewal, Sharon Fekrat
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引用次数: 0
Abstract
Purpose: Retinal imaging offers a noninvasive window into microvascular and neurodegenerative changes, yet its relationship to circulating plasma biomarkers of Alzheimer's disease (AD) remains incompletely understood. We evaluated associations between plasma AD biomarkers and retinal imaging metrics in cognitively normal adults and whether these differ by apolipoprotein E (APOE) ε4 status.
Methods: This cross-sectional analysis included cognitively normal participants prospectively enrolled from the Duke/UNC Alzheimer's Disease Research Center. Eighty-three eyes from 44 participants (20 APOE ε4 carriers, 24 noncarriers) underwent optical coherence tomography (OCT) and OCT angiography (OCTA) within 1 year of plasma sampling. Plasma AD biomarkers were assessed for associations with structural OCT and microvascular OCTA metrics. Linear mixed-effects models adjusted for age, sex, treated hypertension, and years of education were used, with interaction terms for APOE ε4 status followed by stratified analyses.
Results: Nominally significant APOE ε4-dependent interactions were observed between Aβ42/40 and neurofilament light chain (NfL) with ganglion cell-inner plexiform layer (GCIPL) thickness (uncorrected P = 0.026 and P = 0.028). For OCTA, multiple nominally significant APOE ε4-dependent interactions were identified between plasma biomarkers (NfL, pTau217/Aβ42, and pTau217) and perfusion and vessel density across macular regions (uncorrected P = 0.009-0.048). Stratified analyses suggested stronger or more positive relationships in noncarriers, with attenuated or inverse relationships in carriers. None of the associations remained significant after false discovery rate (FDR) correction.
Conclusions: In this exploratory analysis, the APOE ε4 genotype may modify associations between plasma AD biomarkers and retinal structural and microvascular metrics in cognitively normal adults.
Translational relevance: These exploratory findings support further investigation of whether APOE ε4 genotype-status should be considered in future studies integrating retinal imaging and plasma biomarkers in preclinical Alzheimer's disease.
期刊介绍：
Translational Vision Science & Technology (TVST), an official journal of the Association for Research in Vision and Ophthalmology (ARVO), an international organization whose purpose is to advance research worldwide into understanding the visual system and preventing, treating and curing its disorders, is an online, open access, peer-reviewed journal emphasizing multidisciplinary research that bridges the gap between basic research and clinical care. A highly qualified and diverse group of Associate Editors and Editorial Board Members is led by Editor-in-Chief Marco Zarbin, MD, PhD, FARVO.
The journal covers a broad spectrum of work, including but not limited to:
Applications of stem cell technology for regenerative medicine,
Development of new animal models of human diseases,
Tissue bioengineering,
Chemical engineering to improve virus-based gene delivery,
Nanotechnology for drug delivery,
Design and synthesis of artificial extracellular matrices,
Development of a true microsurgical operating environment,
Refining data analysis algorithms to improve in vivo imaging technology,
Results of Phase 1 clinical trials,
Reverse translational ("bedside to bench") research.
TVST seeks manuscripts from scientists and clinicians with diverse backgrounds ranging from basic chemistry to ophthalmic surgery that will advance or change the way we understand and/or treat vision-threatening diseases. TVST encourages the use of color, multimedia, hyperlinks, program code and other digital enhancements.
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