Development of Novel Tau Retinal Tracers for Alzheimer's Disease and other Tauopathies

项目总结 阿尔茨海默病(AD)是一种与年龄相关的疾病，临床上诊断为 痴呆症。这种疾病的定义是淀粉样β蛋白(A)斑块和NFT的形成 由牛磺酸聚集体组成的。尽管tau病理被认为是的次要因素 积累，有人提出，它可能与疾病更准确地相关。 进展和认知变化。异常的tau聚集不仅发生在 阿尔茨海默氏症，但也在一种被称为tauopathies的蛋白质错误折叠疾病家族中。 目前，对表现出认知能力下降症状的个体进行阿尔茨海默病的诊断是一个漫长而 成本高昂的过程，需要几个月到几年的多种测试模式。早期、症状前期 以目前可用的技术，诊断甚至更具挑战性，如果不是不可能的话。 诊断阿尔茨海默病的唯一确定方法是通过尸检分析。验尸前 需要能够在早期无症状阶段可靠地识别AD的诊断，从而实现 在疾病处于晚期之前，患者应在神经科医生的指导下 最大限度地增加治疗干预的机会。此外，一个有用和负担得起的 专注于AD/tauopathy治疗的临床试验需要结果标记物，这些临床试验可能 阻止或逆转疾病的发展。Amydis的目标是通过以下方式解决这些未得到满足的需求 识别眼睛中的tau，作为大脑的窗口，用于早期发现AD/tauopathy。这 提案旨在开发小分子荧光视网膜示踪剂作为一种新的诊断糖尿病的方法 阿尔茨海默氏症和肥胖症。

PROJECT SUMMARY Alzheimer’s disease (AD) is an age-related disease clinically diagnosed by the onset of dementia. This disease is defined by the formation of amyloid-beta (A) plaques and NFTs composed of tau aggregates. Although tau pathology has been considered secondary to A accumulation, it has been proposed that it may correlate more accurately to disease progression and cognitive changes. Abnormal tau aggregation occurs not only in the Alzheimer’s disease, but also in a family of protein-misfolding diseases called tauopathies. Currently, diagnosis of AD in individuals showing symptoms of cognitive decline is a lengthy and costly process, requiring multiple modes of testing over months to years. Early, pre-symptomatic diagnosis is even more challenging, if not impossible, with currently available technology. The only definitive way to diagnose AD is through post-mortem analysis. An ante-mortem diagnostic is needed that can reliably identify AD at the early, asymptomatic stages, enabling patients to get under the guidance of neurologist before the disease is at an advanced stage to maximize the opportunity for therapeutic intervention. Furthermore, a useful and affordable outcome marker is needed for clinical trials focused on therapies for AD/tauopathies that could stop or reverse progression of the disease. Amydis’ goal is to address these unmet needs by identifying tau in the eye, as a window to the brain, for early detection of AD/tauopathies. This proposal aims to develop small molecule fluorescent retinal tracers as a novel diagnostic for Alzheimer’s disease and tauopathies.