{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T12:09:09Z","timestamp":1789560549527,"version":"build-2803163510"},"reference-count":75,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T00:00:00Z","timestamp":1735862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T00:00:00Z","timestamp":1735862400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>\n                      Late\u2010onset Alzheimer's Disease (LOAD) is the predominant form of Alzheimer's disease (AD), and apolipoprotein E (\n                      <jats:italic>APOE<\/jats:italic>\n                      ) \u03b54 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\u2010dependent retinal impairments in humanized\n                      <jats:italic>APOE4<\/jats:italic>\n                      \u2010knock\u2010in (KI) and\n                      <jats:italic>APOE3<\/jats:italic>\n                      \u2010KI mice developed by the Model Organism Development and Evaluation for Late\u2010Onset Alzheimer's Disease (MODEL\u2010AD) consortium.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>All the experiments were performed on 52\u2010 to 57\u2010week\u2010old 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      <jats:italic>APOE4<\/jats:italic>\n                      \u2010KI mice showed impaired retinal structure, vasculature, function, vision, increased gliosis and neuroinflammation, and downregulation of synaptogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 allele is associated with increased susceptibility to retinal degeneration compared to the\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b53 allele.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            Apolipoprotein E (APOE)\n                            <jats:italic>4<\/jats:italic>\n                            mice exhibit structural and functional deficits of the retina.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            The retinal defects in\n                            <jats:italic>APOE4<\/jats:italic>\n                            mice are attributed to increased neuroinflammation.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:italic>APOE4<\/jats:italic>\n                            mice show a unique retinal transcriptome, yet with key brain similarities.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The retina offers a non\u2010invasive biomarker for the detection and monitoring of Alzheimer's disease.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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