A noninvasive optical imaging of retinal amyloid beta deposits in AD patients

描述(申请人提供)：阿尔茨海默病(AD)是一种进行性的、总是致命的退行性痴呆，也是目前影响超过500万美国人的最常见的痴呆症形式。生活质量和经济成本是巨大的，据估计，2012年美国医疗保健支出超过2000亿美元，加上1500多万美国人的无偿护理，价值2100亿美元。AD的非侵入性诊断，特别是早期诊断，是有效治疗的关键，也是一个迫切的未得到满足的需求。由于现有的非侵入性脑成像技术无法提供微米级变化的足够细节，组织评估在特异性和分辨率方面都受到限制，目前AD最明确的诊断是在尸检时。我们应用的核心是识别AD患者死后和活体视网膜中的淀粉样β蛋白(Abeta)斑块，这是AD病理的特征，可能在疾病的早期阶段也是如此。我们的Cedars-Sinai研究团队发表的一项研究证明，在AD患者的死后视网膜中发现了Abeta斑块，该团队也是NeuroVision，LLC的创始成员。(NVI)。我们团队进一步开发了一种新的非侵入性视网膜成像方法，通过在AD转基因小鼠模型中标记姜黄素来检测这些斑块，从而能够以前所未有的高灵敏度和特异度对Abeta斑块进行体内成像。视网膜成像的可行性、成本和易用性的基本优势使其成为一种有吸引力的方式，在明确的AD早期诊断和监测方面具有巨大的潜力。这项STTR拨款申请的主要目标是创建和验证一种非侵入性视网膜成像方法，以检测AD和轻度认知障碍患者视网膜中的Abeta沉积。这一应用程序的一大优势依赖于Cedars-Sinai研究小组(专门研究视网膜AD病理成像)、KB图像解决方案公司(图像处理专家)和NeuroVision Image LLC(眼科设备和成像系统商业化的领先者)之间的紧密合作。它有可能开发、验证并最终商业化一种新的非侵入性视网膜Abeta成像技术，以促进AD的诊断，具体目标如下：1)检查AD患者死后视网膜中Abeta斑块和视网膜层的地理位置，以指导后续的成像方案；2)优化姜黄素荧光成像设备和软件，并提高Abeta斑块检测的信号水平；以及3)进行初步的临床成像研究，并使用数据自动计算视网膜 淀粉样蛋白指数(RAI)，视网膜中淀粉样蛋白的定量测量。由于目前在获得明确的AD早期诊断测试方面存在局限性，拟议研究的商业影响可能会对市场产生重大影响。

DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is a progressive and invariably fatal degenerative dementia and the most common form of dementia that currently affects over 5 million Americans. The quality of life and economic costs are significant with estimated U.S. health care payments of over $200 billion in 2012, plus unpaid care by over 15 million Americans that is valued at $210 billion. A noninvasive diagnosis of AD and especially at early stage is essential for effective treatment and presents an urgent unmet need. Since existing noninvasive brain imaging technologies cannot provide sufficient detail about micrometer-size changes, tissue evaluation is limited in both specificity and resolution, and the most definitive diagnosis of AD currently comes at time of autopsy. At the core of our application is the identification of amyloid-beta protein (Abeta) plaques, characteristic of AD pathology, in postmortem and live human retina of AD patients, and possibly at early stages of the disease. The discovery of Abeta plaques in postmortem retinas of AD patients was demonstrated in a study published by our Cedars-Sinai research team, which are also the founding members of NeuroVision, LLC. (NVI). Further development of a novel noninvasive retinal imaging approach by our team to detect these plaques by curcumin labeling in live AD transgenic mouse models, allowed for the in vivo imaging of Abeta plaques at unprecedented high sensitivity and specificity. The fundamental advantages of feasibility, cost and ease-of use of retinal imaging make it an attractive modality, with great potential for unequivocal early diagnosis and monitoring of AD. The principal goal of this STTR grant application is to create and validate a noninvasive retinal imaging methodology to detect Abeta deposits in the retina of AD and mild cognitive impairment patients. A major strength of this application relies on the tight collaboration between the Cedars-Sinai research group (specializing in imaging retinal AD pathology), KB Imaging Solutions LLC (image processing experts), and NeuroVision Imaging LLC (leaders in commercializing ophthalmic devices and imaging systems). It has the potential to develop, validate, and eventually commercialize a novel noninvasive retinal Abeta imaging technology to facilitate AD diagnosis, with the following specific objectives: 1) To examine the geographic location of Abeta plaques and retinal layers in the postmortem retina of AD patients so as to guide the subsequent imaging protocol; 2) To optimize the imaging device and software for curcumin fluorescence and improve signal level for the detection of Abeta plaques; and 3) To perform an initial clinical imaging study and use the data to automate the calculation of a Retinal Amyloid Index (RAI), a quantitative measure of amyloid in the retina. With the current limitations in obtaining a definitive and early diagnostic test for AD, the commercial implications of the proposed study have the potential to make a significant impact on the market.