{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T19:17:49Z","timestamp":1787944669282,"version":"build-2784847793"},"reference-count":64,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute on Aging of the National Institutes of Health","award":["P30AG072958"],"award-info":[{"award-number":["P30AG072958"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Evaluating noninvasive, accessible ocular and blood-based biomarkers could aid in early risk stratification and disease detection during the preclinical phase of Alzheimer\u2019s disease. This study investigates associations between plasma biomarkers of neurodegeneration and retinal structural and microvasculature parameters in cognitively normal adults with familial or genetic risk factors for Alzheimer\u2019s disease. Methods: Forty-one participants underwent plasma sampling for glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), amyloid-beta42 (\u03b242), amyloid-\u03b242\/40 ratio, and phosphorylated-tau217 (p-tau217), and also underwent optical coherence tomography (OCT) and OCT angiography (OCTA) imaging. Apolipoprotein E genotyping and family history of Alzheimer\u2019s disease were recorded. Generalized estimating equations adjusting for age, sex, race, treated hypertension, Alzheimer\u2019s disease family history, and APOE \u03b54 carrier status assessed associations between plasma biomarker concentrations and OCT and OCTA measurements. Results: Higher plasma GFAP and NfL concentrations were significantly associated with reduced superficial capillary plexus perfusion density and vessel density on macular OCTA. In additional analyses restricted to participants with plasma biomarker and retinal imaging assessments obtained within 9 months, associations with GFAP remained significant, whereas NfL associations no longer remained significant after correction for multiple comparisons. Conclusions: Retinal OCTA and OCT metrics may reflect general neurovascular aging in cognitively normal individuals with familial or genetic risk factors for Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.3390\/diagnostics16172764","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T18:33:52Z","timestamp":1787942032000},"page":"2764","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma Glial Fibrillary Acidic Protein and Neurofilament Light Chain Concentrations Are Inversely Associated with Retinal Microvascular Perfusion and Vessel Density in Cognitively Normal Individuals with Familial or Genetic Risk Factors for Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6587-1089","authenticated-orcid":false,"given":"Wufan","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Duke University School of Medicine, Durham, NC 27710, USA"},{"name":"Eye Multimodal Imaging in Neurodegenerative Disease (iMIND) Study Group, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7072-2023","authenticated-orcid":false,"given":"Michael Y.","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Duke University School of Medicine, Durham, NC 27710, USA"},{"name":"Eye Multimodal Imaging in Neurodegenerative Disease (iMIND) Study Group, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7151-0492","authenticated-orcid":false,"given":"Hemal","family":"Patel","sequence":"additional","affiliation":[{"name":"Eye Multimodal Imaging in Neurodegenerative Disease (iMIND) Study Group, Durham, NC 27710, USA"},{"name":"Wills Eye Hospital, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Heather E.","family":"Whitson","sequence":"additional","affiliation":[{"name":"Eye Multimodal Imaging in Neurodegenerative Disease (iMIND) Study Group, Durham, NC 27710, USA"},{"name":"Department of Neurology, Duke University School of Medicine, Durham, NC 27710, USA"},{"name":"Duke\/UNC Alzheimer\u2019s Disease Research Center (ADRC), Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8793-2489","authenticated-orcid":false,"given":"Kim G.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Eye Multimodal Imaging in Neurodegenerative Disease (iMIND) Study Group, Durham, NC 27710, USA"},{"name":"Department of Neurology, Duke University School of Medicine, Durham, NC 27710, USA"},{"name":"Duke\/UNC Alzheimer\u2019s Disease Research Center (ADRC), Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Dilraj S.","family":"Grewal","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Duke University School of Medicine, Durham, NC 27710, USA"},{"name":"Eye Multimodal Imaging in Neurodegenerative Disease (iMIND) Study Group, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Sharon","family":"Fekrat","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Duke University School of Medicine, Durham, NC 27710, USA"},{"name":"Eye Multimodal Imaging in Neurodegenerative Disease (iMIND) Study Group, Durham, NC 27710, USA"},{"name":"Department of Neurology, Duke University School of Medicine, Durham, NC 27710, USA"},{"name":"Duke\/UNC Alzheimer\u2019s Disease Research Center (ADRC), Durham, NC 27710, USA"},{"name":"Duke University Medical Center, 2351 Erwin Road, Durham, NC 27705, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"ref_1","unstructured":"(2019). 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