Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
Retinal dysfunction in APOE4 knock-in mouse model of Alzheimer's disease.
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Abhyankar Surabhi D, Luo Qianyi, Hartman Gabriella D, Mahajan Neha, Corson Timothy W, Oblak Adrian L, Lamb Bruce T, Bhatwadekar Ashay D
Аннотация
INTRODUCTION: 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.
METHODS: 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.
RESULTS: APOE4-KI mice showed impaired retinal structure, vasculature, function, vision, increased gliosis and neuroinflammation, and downregulation of synaptogenesis.
DISCUSSION: The APOE ε4 allele is associated with increased susceptibility to retinal degeneration compared to the APOE ε3 allele.
HIGHLIGHTS: 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.
METHODS: 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.
RESULTS: APOE4-KI mice showed impaired retinal structure, vasculature, function, vision, increased gliosis and neuroinflammation, and downregulation of synaptogenesis.
DISCUSSION: The APOE ε4 allele is associated with increased susceptibility to retinal degeneration compared to the APOE ε3 allele.
HIGHLIGHTS: 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.