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

IF 11.1 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-10-09 DOI:10.1002/alz.70745

William Robert Kwapong, Ning Wu, Weihong Lin, Jianing Shen, Youjie Wang, Jiajing Qian, Caiyun Wen, Xiaoqian Luan, Yuntao Liu, Haoran Cheng, Huihua Qiu, Carol Y. Cheung, Chunwen Zheng, Yinhe Liu, Yunjun Yang, Vincent Mok, Zhen Wang

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Abstract

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) is sensitive to microvascular damage and can differentiate Alzheimer's disease (AD) from cognitively unimpaired controls.
Retinal microvascular damage in AD is associated with phosphorylated tau [p-tau]181, p-tau217, p-tau217/amyloid beta (Aβ)42, and increased amyloid burden (lower Aβ42 and Aβ42/40).
Retinal microvascular damage in AD is associated with increased cerebral small vessel burden.

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阿尔茨海默病的视网膜微血管改变：血浆生物标志物与脑血管病理的联系

背景：通过眼底彩色摄影（CFP）检测到的视网膜微血管改变可能反映阿尔茨海默病（AD）的大脑微血管病理。然而，它们与基于血液的生物标志物和脑血管疾病（SVD）的关联尚不清楚。方法本横断面研究纳入72例AD患者和82例认知未受损（CU）对照。参与者接受了CFP、血浆生物标志物分析（淀粉样蛋白β [Aβ]42、Aβ42/40、磷酸化tau [p‐tau]181、p‐tau217）和3T磁共振成像。视网膜微血管指标（血管密度[VD]、分形维数[FD]）与SVD指标（白质高强度[WMHs]、SVD负担）和内侧颞叶萎缩（MTA）一起进行分析。结果与CU相比，ad患者的VD和FD均显著降低（p < 0.001），诊断准确性高（VD曲线下面积：0.969；FD曲线下面积：0.904）。视网膜微血管损伤与血浆生物标志物（Aβ42、Aβ42/40降低；p - tau181、p - tau217升高；均p <； 0.05）和SVD神经影像学标志物（WMHs、MTA；均p <； 0.05）相关。载脂蛋白E ε4携带者视网膜微血管损伤更为严重（p < 0.001）。通过CFP检测的视网膜微血管改变与阿尔茨海默病特异性蛋白病变和脑血管病理有关，支持CFP作为一种可扩展的、非侵入性的阿尔茨海默病生物标志物发现工具。通过彩色眼底摄影（CFP）检测视网膜微血管对微血管损伤很敏感，可以将阿尔茨海默病（AD）与认知功能未受损的对照组区分出来。AD视网膜微血管损伤与磷酸化tau [p‐tau]181、p‐tau217、p‐tau217/淀粉样蛋白β (Aβ)42和淀粉样蛋白负荷增加（降低Aβ42和Aβ42/40）有关。AD患者视网膜微血管损伤与脑血管负荷增加有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.