Multimodal Retinal Imaging Correlates With Brain Atrophy and Plasma Biomarkers in Alzheimer's Disease.
6 affiliations
- 1Department of Geriatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
- 2School of Mental Health, Wenzhou Medical University, Wenzhou, China.
- 3Department of Neurology, West China Hospital, Sichuan University, Chengdu, China.
- 4Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
- 5Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
- 6Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Abstract
Purpose
To investigate retinal structural and microvascular changes in Alzheimer's disease (AD) and evaluate their associations with neuroimaging markers, plasma biomarkers, and cognitive impairment.Methods
This cross-sectional study included 181 participants (95 with AD and 86 cognitively unimpaired controls). AD diagnosis was established according to National Institute on Aging-Alzheimer's Association criteria with positive amyloid-β positron emission tomography imaging. Retinal structure and microvasculature were assessed using swept-source optical coherence tomography (OCT) and OCT angiography (OCTA). Cortical thickness and gray matter volume were quantified using structural magnetic resonance imaging. Plasma Aβ42 and phosphorylated tau-217 (p-tau217) were measured, and cognitive function was evaluated using the Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA).Results
Compared with controls, patients with AD demonstrated reduced retinal nerve fiber layer, ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer, and outer retinal layer thicknesses, together with lower superficial vascular complex (SVC) and deep vascular complex densities (all P < 0.001). GCIPL thickness and SVC density were associated with cortical atrophy in AD-vulnerable regions, including temporal, parietal, and occipital cortices. Lower plasma Aβ42 levels were associated with reduced retinal layer thickness and vascular density, whereas higher p-tau217 levels were associated with reduced outer retinal layer thickness and SVC density. GCIPL thickness showed the strongest association with cognitive performance, while lower SVC density was associated with poorer MoCA scores. APOE ε4 carriers exhibited greater GCIPL thinning, reduced retinal vascular density, and more extensive cortical abnormalities despite similar plasma Aβ42 and p-tau217 levels.Conclusions
Retinal neuronal and microvascular alterations are associated with AD-related molecular pathology, cerebral neurodegeneration, APOE ε4-related vulnerability, and cognitive impairment. OCT/OCTA may provide a noninvasive adjunct approach for characterizing neurodegenerative and neurovascular changes in AD.Translational relevance
Retinal imaging may provide a scalable and noninvasive approach for detecting and monitoring AD pathology.
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BibTeX
@article{luan2026multimodal,
title = {{Multimodal Retinal Imaging Correlates With Brain Atrophy and Plasma Biomarkers in Alzheimer's Disease.}},
author = {Xiaoqian Luan and Jianing Shen and Youjie Wang and Huihua Qiu and Haoran Cheng and Chunwen Zheng and Suqing Hu and Caiyun Wen and Guoquan Cao and William Robert Kwpaong and Zhen Wang},
journal = {Translational vision science \& technology},
year = {2026},
month = oct,
doi = {10.1167/tvst.15.10.24},
url = {https://europepmc.org/article/MED/42885984},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Multimodal Retinal Imaging Correlates With Brain Atrophy and Plasma Biomarkers in Alzheimer's Disease.
AU - Xiaoqian Luan
AU - Jianing Shen
AU - Youjie Wang
AU - Huihua Qiu
AU - Haoran Cheng
AU - Chunwen Zheng
AU - Suqing Hu
AU - Caiyun Wen
AU - Guoquan Cao
AU - William Robert Kwpaong
AU - Zhen Wang
PY - 2026
DA - 2026/10/01
JO - Translational vision science & technology
DO - 10.1167/tvst.15.10.24
UR - https://europepmc.org/article/MED/42885984
AB - Purpose To investigate retinal structural and microvascular changes in Alzheimer's disease (AD) and evaluate their associations with neuroimaging markers, plasma biomarkers, and cognitive impairment.Methods This cross-sectional study included 181 participants (95 with AD and 86 cognitively unimpaired controls). AD diagnosis was established according to National Institute on Aging-Alzheimer's Association criteria with positive amyloid-β positron emission tomography imaging. Retinal structure and microvasculature were assessed using swept-source optical coherence tomography (OCT) and OCT angiography (OCTA). Cortical thickness and gray matter volume were quantified using structural magnetic resonance imaging. Plasma Aβ42 and phosphorylated tau-217 (p-tau217) were measured, and cognitive function was evaluated using the Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA).Results Compared with controls, patients with AD demonstrated reduced retinal nerve fiber layer, ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer, and outer retinal layer thicknesses, together with lower superficial vascular complex (SVC) and deep vascular complex densities (all P < 0.001). GCIPL thickness and SVC density were associated with cortical atrophy in AD-vulnerable regions, including temporal, parietal, and occipital cortices. Lower plasma Aβ42 levels were associated with reduced retinal layer thickness and vascular density, whereas higher p-tau217 levels were associated with reduced outer retinal layer thickness and SVC density. GCIPL thickness showed the strongest association with cognitive performance, while lower SVC density was associated with poorer MoCA scores. APOE ε4 carriers exhibited greater GCIPL thinning, reduced retinal vascular density, and more extensive cortical abnormalities despite similar plasma Aβ42 and p-tau217 levels.Conclusions Retinal neuronal and microvascular alterations are associated with AD-related molecular pathology, cerebral neurodegeneration, APOE ε4-related vulnerability, and cognitive impairment. OCT/OCTA may provide a noninvasive adjunct approach for characterizing neurodegenerative and neurovascular changes in AD.Translational relevance Retinal imaging may provide a scalable and noninvasive approach for detecting and monitoring AD pathology.
SN - 2164-2591
ER -