{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:10:07Z","timestamp":1792595407725,"version":"4.5.0"},"reference-count":76,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T00:00:00Z","timestamp":1759622400000},"content-version":"vor","delay-in-days":34,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIA R01 AG061138"],"award-info":[{"award-number":["NIA R01 AG061138"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Impaired amyloid beta (A\u03b2) clearance contributes to sporadic Alzheimer's disease (AD). This study investigated retinal A\u03b2 clearance involving neuronal, glial, and vascular interactions at the inner blood\u2013retina barrier (iBRB), a functional analog of the blood\u2013brain barrier (BBB).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Retinal wholemounts from AD donors and controls were analyzed alongside transgenic amyloid precursor protein\/presenilin 1 (APP\u2010PS1) and non\u2010carrier control mouse retinal cross\u2010sections using three\u2010 and two\u2010dimensional ex vivo imaging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>AD neuroretinas displayed increased larger A\u03b242 deposits, microglial elongation, and substantial reductions in macroglial support and water channel expression. The uptake of soluble A\u03b2 oligomers (SA\u03b2Os) by peripheral macrophage\u2010like, A\u03b2\u2010binding myeloid lineage cells was also diminished. In APP\u2010PS1 mice, elevated glia levels, alongside increased APP\/A\u03b2 expression, suggest gliosis and failures in clearance processes with disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Ex vivo three\u2010dimensional retinal imaging at the iBRB provides novel insights into A\u03b2 clearance in AD, which is difficult to replicate in ex vivo brain studies at the BBB.<\/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>Impaired clearance mechanisms play a key role in sporadic AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The iBRB serves as a functional analog to the BBB.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>At the iBRB, the glymphatic system and microglial phagocytosis help mitigate A\u03b2 burden.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Peripheral macrophage\u2010like myeloid lineage cells may aid SA\u03b2O clearance.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The imaging plane (surface vs cross\u2010section) may affect AD pathogenesis findings.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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