{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T22:38:10Z","timestamp":1792881490164,"version":"4.5.0"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Retinal microvascular alterations, detectable via color fundus photography (CFP), may reflect cerebral microvascular pathology in Alzheimer's disease (AD). However, their associations with blood\u2010based biomarkers and cerebral small vessel disease (SVD) remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>This cross\u2010sectional study included 72 AD patients and 82 cognitively unimpaired (CU) controls. Participants underwent CFP, plasma biomarker analysis (amyloid beta [A\u03b2]42, A\u03b242\/40, phosphorylated tau [p\u2010tau]181, p\u2010tau217), and 3T magnetic resonance imaging. Retinal microvascular metrics (vessel density [VD], fractal dimension [FD]) were analyzed alongside SVD markers (white matter hyperintensities [WMHs], SVD burden) and medial temporal lobe atrophy (MTA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      AD patients exhibited significantly reduced VD and FD compared to CU (all\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001), with strong diagnostic accuracy (area under the curve: 0.969 for VD; 0.904 for FD). Retinal microvascular impairment correlated with plasma biomarkers (lower A\u03b242, A\u03b242\/40; elevated p\u2010tau181, p\u2010tau217; all\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05) and neuroimaging markers of SVD (WMHs, MTA; all\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05). Apolipoprotein E \u03b54 carriers showed more severe retinal microvascular damage (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Retinal microvascular alterations, assayed via CFP, are linked to AD\u2010specific proteinopathy and cerebrovascular pathology, supporting CFP as a scalable, non\u2010invasive tool for AD biomarker discovery.<\/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>Retinal microvasculature assayed via color fundus photography (CFP) is sensitive to microvascular damage and can differentiate Alzheimer's disease (AD) from cognitively unimpaired controls.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Retinal microvascular damage in AD is associated with phosphorylated tau [p\u2010tau]181, p\u2010tau217, p\u2010tau217\/amyloid beta (A\u03b2)42, and increased amyloid burden (lower A\u03b242 and A\u03b242\/40).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Retinal microvascular damage in AD is associated with increased cerebral small vessel burden.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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Laboratory of Alzheimer's Disease of Zhejiang Province  Wenzhou China"},{"name":"Healthcare Center The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Wenzhou Key Laboratory of Intelligent Prevention and Active Health for Aging\u2010Related Chronic Diseases The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianing","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Geriatrics The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajing","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Geriatrics The First 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