The last decade has seen a substantial increase in research focused on the identification, development, and validation of diagnostic and prognostic retinal biomarkers for Alzheimer's disease (AD). Sensitive retinal biomarkers may be advantageous because they are cost and time efficient, non‐invasive, and present a minimal degree of patient risk and a high degree of accessibility. Much of the work in this area thus far has focused on distinguishing between symptomatic AD and/or mild cognitive impairment (MCI) and cognitively normal older adults. Minimal work has been done on the detection of preclinical AD, the earliest stage of AD pathogenesis characterized by the accumulation of cerebral amyloid absent clinical symptoms of MCI or dementia. The following review examines retinal structural changes, proteinopathies, and vascular alterations that have been proposed as potential AD biomarkers, with a focus on studies examining the earliest stages of disease pathogenesis. In addition, we present recommendations for future research to move beyond the discovery phase and toward validation of AD risk biomarkers that could potentially be used as a first step in a multistep screening process for AD risk detection.

中文翻译：

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为阿尔茨海默病的早期阶段开发视网膜生物标志物：我们知道什么，我们不知道什么，以及如何前进

在过去十年中，针对阿尔茨海默病 (AD) 诊断和预后视网膜生物标志物的识别、开发和验证的研究显着增加。敏感的视网膜生物标志物可能是有利的，因为它们具有成本和时间效率、非侵入性、最低程度的患者风险和高度的可及性。迄今为止，该领域的大部分工作都集中在区分有症状的 AD 和/或轻度认知障碍 (MCI) 与认知正常的老年人。对临床前 AD 的检测已经做了最少的工作，AD 发病机制的最早阶段的特征是脑淀粉样蛋白的积累，而没有 MCI 或痴呆的临床症状。以下综述检查了视网膜结构变化、蛋白质病、和血管改变已被提议作为潜在的 AD 生物标志物，重点研究检查疾病发病机制的最早阶段。此外，我们为未来的研究提出了建议，以超越发现阶段并验证 AD 风险生物标志物，这些生物标志物可能用作 AD 风险检测多步筛选过程的第一步。