Abhyankar Surabhi D, Luo Qianyi, Hartman Gabriella D, Mahajan Neha, Corson Timothy W, Oblak Adrian L, Lamb Bruce T, Bhatwadekar Ashay D
Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Alzheimers Dement. 2025 Feb;21(2):e14433. doi: 10.1002/alz.14433. Epub 2025 Jan 3.
Late-onset Alzheimer's Disease (LOAD) is the predominant form of Alzheimer's disease (AD), and apolipoprotein E (APOE) ε4 is a strong genetic risk factor for LOAD. As an integral part of the central nervous system, the retina displays a variety of abnormalities in LOAD. Our study is focused on age-dependent retinal impairments in humanized APOE4-knock-in (KI) and APOE3-KI mice developed by the Model Organism Development and Evaluation for Late-Onset Alzheimer's Disease (MODEL-AD) consortium.
All the experiments were performed on 52- to 57-week-old mice. The retina was assessed by optical coherence tomography, fundoscopy, fluorescein angiography, electroretinography, optomotor response, gliosis, and neuroinflammation. mRNA sequencing was performed to find molecular pathways.
APOE4-KI mice showed impaired retinal structure, vasculature, function, vision, increased gliosis and neuroinflammation, and downregulation of synaptogenesis.
The APOE ε4 allele is associated with increased susceptibility to retinal degeneration compared to the APOE ε3 allele.
Apolipoprotein E (APOE)4 mice exhibit structural and functional deficits of the retina. The retinal defects in APOE4 mice are attributed to increased neuroinflammation. APOE4 mice show a unique retinal transcriptome, yet with key brain similarities. The retina offers a non-invasive biomarker for the detection and monitoring of Alzheimer's disease.
晚发性阿尔茨海默病（LOAD）是阿尔茨海默病（AD）的主要形式，载脂蛋白E（APOE）ε4是LOAD的一个强大遗传风险因素。视网膜作为中枢神经系统的一个组成部分，在LOAD中表现出多种异常。我们的研究聚焦于由晚发性阿尔茨海默病模式生物开发与评估（MODEL-AD）联盟培育的人源化APOE4基因敲入（KI）和APOE3-KI小鼠中与年龄相关的视网膜损伤。
所有实验均在52至57周龄的小鼠上进行。通过光学相干断层扫描、检眼镜检查、荧光素血管造影、视网膜电图、视动反应、胶质增生和神经炎症来评估视网膜。进行mRNA测序以寻找分子途径。
APOE4-KI小鼠表现出视网膜结构、血管系统、功能、视力受损，胶质增生和神经炎症增加，以及突触发生下调。
与APOE ε3等位基因相比，APOE ε4等位基因与视网膜变性易感性增加有关。
载脂蛋白E（APOE）4小鼠表现出视网膜的结构和功能缺陷。APOE4小鼠的视网膜缺陷归因于神经炎症增加。APOE4小鼠表现出独特的视网膜转录组，但与大脑有关键相似之处。视网膜为阿尔茨海默病的检测和监测提供了一种非侵入性生物标志物。
