Alzheimer disease biomarkers in lens

我们的工作表明，专注于阿尔茨海默病β-淀粉样前体蛋白(AbetaPP)的基本神经元特异性细胞生物学过程在晶状体中有着惊人的共享程度，并提供了证据表明Abeta病理是类似于阿尔茨海默病(AD)的白内障形成的关键因素。此外，我们实验室和最近其他实验室的研究表明，年龄相关性白内障中的Abeta病理与AD患者和动物模型中脑内Abeta病理的相应变化有非常密切的联系。这些关联与晶状体和大脑老化过程中压力的广泛共享的生物素质是一致的，我们最初的研究也表明了这一点。现在，我们将研究在白内障形成的早期疾病阶段晶状体中特定形式的Abeta病理的产生，并将其与脑内相应的Abeta病理变化的发生和发展的关系进行表征。具体地说，我们将表征我们最近在晶状体中发现的新的晶状体Abeta生物标记物，并探索它们在白内障早期诊断中的用途，并研究这些生物标记物在监测大脑中发生的相关变化方面的使用。我们的第二个主要目标也是致力于开发我们最近敏感的基于激光的技术的新应用，以检测晶状体中的这些Abeta生物标记物，用于诊断早期白内障，并将确定其告知大脑相关变化的能力。这一仪器已经为我们提供了一个重要的新研究工具，帮助我们了解AD病理在白内障中的作用以及与脑的关系。这项工作已经使人们认识到，AD研究中的“主力”模型也提供了与年龄相关的白内障的重要模型。我们的目标是严格表征晶状体中Abeta生物标志物的增加，以了解它们在人类晶状体和我们的动物模型早期白内障形成中的作用，并研究晶状体中产生的产物与大脑中相应的病理发生的关系。这种严格的非侵入性技术具有在形成明显的光散射或蛋白质聚集之前检测早期白内障的巨大潜力，这些散射或蛋白质聚集目前是白内障诊断和监测大脑变化的标志。这些研究建立在我们早期研究的基础上，以了解AbetaPP和Abeta在晶状体中的作用，这已经为理解白内障及其与大脑的联系提供了新的和具体的概念基础。

Our work has demonstrated that fundamental neuron-specific cell biology processes that are focused on the Alzheimer beta-amyloid precursor protein (AbetaPP) are shared in the lens to a striking degree, and provided evidence that Abeta pathology is a key element in cataract formation similar to Alzheimer's disease (AD). Further, studies from our lab and recently others indicate that Abeta pathology in age-related cataract has a remarkably close association with corresponding changes in Abeta pathology in the brain in AD patients, and in animal models. These associations are consistent with an extensively shared biological diathesis for stress during aging in lens and brain and were indicated by our original studies. Now we will investigate the production of specific forms of Abeta pathology in the lens during early disease stages of cataract formation, and will also characterize its relationship with the onset and development of corresponding changes in Abeta pathology in brain. Specifically, we will characterize novel lens Abeta biomarkers we recently identified in the lens and explore their use for the early diagnosis of cataract, and investigate the use of these biomarkers for monitoring associated changes occurring in brain. Our second major goal is also to work to develop our recent novel application of sensitive laser-based technology to detect these Abeta biomarkers in the lens for the diagnosis of early stages of cataract, and will determine its ability to inform about related changes in the brain. This instrument is already providing us with a critical new research tool to help us understand the role of AD pathology in cataracts and relationship with brain. This work has already led to an understanding that 'workhorse' models in AD research also provide important models of age-related cataract. Our goal is to rigorously characterize Abeta biomarker increases in lens to understand their role in early cataractogenesis in human lens and our animal model, and to investigate onset of production in lens with onset of corresponding pathology in brain. This strictly non-invasive technology has significant potential to detect early stages of cataract prior to formation of significant light scattering or protein aggregation that presently are hallmarks of cataract diagnosis and efforts to monitor changes in brain. These studies build on our earlier studies to understand the role of AbetaPP and Abeta in the lens which are already providing a new and specific conceptual basis for understanding cataract and its links with the brain.