Retinal microvascular alterations in Alzheimer's disease: Linking blood plasma biomarkers and cerebral small vessel pathology

作者：William Robert Kwapong, Ning Wu, Weihong Lin, Jianing Shen, Youjie Wang, Jingjing Qian, Caiyun Wen, Xiaoqian Luan, Yuntao Liu, Haoran Cheng, Huihua Qiu, Carol Yim-Lui Cheung, Chunwen Zheng, Yinhe Liu, Yunjun Yang, Vincent Mok, Zhen Wang · 发表于：Alzheimer s & Dementia · 年份：2025 · DOI：10.1002/alz.70745 · 被引用次数：11 · 研究领域：Retinal Imaging and Analysis、Glaucoma and retinal disorders、Dementia and Cognitive Impairment Research

BACKGROUND: Retinal microvascular alterations, detectable via color fundus photography (CFP), may reflect cerebral microvascular pathology in Alzheimer's disease (AD). However, their associations with blood-based biomarkers and cerebral small vessel disease (SVD) remain unclear. METHODS: This cross-sectional study included 72 AD patients and 82 cognitively unimpaired (CU) controls. Participants underwent CFP, plasma biomarker analysis (amyloid beta [Aβ]42, Aβ42/40, phosphorylated tau [p-tau]181, p-tau217), 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). RESULTS: AD patients exhibited significantly reduced VD and FD compared to CU (all p < 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 Aβ42, Aβ42/40; elevated p-tau181, p-tau217; all p < 0.05) and neuroimaging markers of SVD (WMHs, MTA; all p < 0.05). Apolipoprotein E ε4 carriers showed more severe retinal microvascular damage (p < 0.001). DISCUSSION: Retinal microvascular alterations, assayed via CFP, are linked to AD-specific proteinopathy and cerebrovascular pathology, supporting CFP as a scalable, non-invasive tool for AD biomarker discovery. HIGHLIGHTS: Retinal microvasculature assayed via color fundus photography (CFP)...