Alzheimer disease biomarkers in lens

我们的工作已经证明，基本的神经元特异性细胞生物学过程，集中在阿尔茨海默氏症β-淀粉样前体蛋白（AbetaPP）是共享的透镜到一个惊人的程度，并提供证据表明，Abeta病理是一个关键因素，在白内障形成类似于阿尔茨海默氏症（AD）。此外，来自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病理学与AD患者和动物模型中大脑中Abeta病理学的相应变化具有非常密切的相关性。这些关联与透镜和大脑老化过程中广泛共享的应激生物素质一致，并且由我们的原始研究表明。现在，我们将研究在白内障形成的早期疾病阶段，透镜中特定形式的Abeta病理学的产生，并且还将表征其与脑中Abeta病理学的相应变化的发生和发展的关系。具体而言，我们将表征我们最近在透镜中鉴定的新型透镜Abeta生物标志物，并探索其用于白内障早期诊断的用途，并研究这些生物标志物用于监测脑中发生的相关变化的用途。我们的第二个主要目标也是致力于开发我们最近的基于敏感激光的技术的新应用，以检测透镜中的这些Abeta生物标志物，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。该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病理学在白内障中的作用以及与大脑的关系。这项工作已经使人们认识到，AD研究中的“主力”模型也提供了年龄相关性白内障的重要模型。我们的目标是严格表征透镜中Abeta生物标志物的增加，以了解它们在人类透镜和我们的动物模型中的早期白内障发生中的作用，并研究透镜中产生的开始以及脑中相应病理的开始。这种严格的非侵入性技术具有在形成显著的光散射或蛋白质聚集之前检测早期白内障的显著潜力，这些光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在透镜中的作用，这些研究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.