Near infrared Fluorescence Ocular Imaging of Soluble Amyloid Beta Species

检测可溶性淀粉样β蛋白(Aβ)是阿尔茨海默病早期初步筛查的关键 疾病(AD)。尽管科学家开发治疗阿尔茨海默病的有效药物非常令人沮丧， 越来越多的证据表明，早期干预可能是预防/减缓病情发展的关键，而早期干预可能是预防/减缓病情发展的关键。 症状期可能是未来AD治疗的最佳干预窗口。最近的研究表明 可溶性Aβ(Saβ)物种，如低聚物，比不溶Aβ(Insaβ)斑块更具神经毒性，以及 有可能作为AD症状前阶段的生物标志物。因此，检测Saβ是一种 AD早期诊断和治疗监测的基本要求。 近红外荧光眼科成像(NIRFOI)有可能用于早期初步筛查 广告。虽然MRI和PET等成像技术对AD的诊断非常有用，但它们也是 初步筛查的费用很高。相比之下，近红外荧光(NIRF)成像由于其低成本， 操作简单、处理能力强、数据分析直观，是成像方法之一 最有潜力的。然而，NIRF脑成像在AD的临床应用中几乎没有潜力 诊断，由于近红外光对组织的穿透限制。尽管如此，视网膜/眼睛仍可用作 大脑之窗，而NIRF眼部成像(NIRFOI)是一种自然的替代方法，因为1)优秀的 2)视网膜中的β病理与脑Aβ病理相关。我们的预赛 结果表明，用红外光谱检测小鼠眼睛中的AβS是可行的。由于成本低，操作方便， 并且灵敏度高，我们认为NIRFOI具有检测早期Aβ病理的临床潜力，并且 可用于将来对症状前期AD患者的初步筛查。在这 应用，我们提出了NIRFOI的概念，据我们所知，这一概念还没有被探索过。在……里面 在这项提议中，我们将使用我们的探针CRANAD-102来验证NIRFOI，用于检测眼睛中的Saβ，并用于 监测AD小鼠病情进展和药物治疗过程中Sa-β的变化。

Detecting soluble amyloid beta (Aβ) species is a key for early preliminary screening of Alzheimer's disease (AD). Although it has been extremely frustrating for scientists to develop effective drugs for AD, mounting evidence indicates that early intervention is the likely key to prevent/slow the progression, and pre- symptomatic stage could be the best intervention window for AD treatment in the future. Recent studies show that soluble Aβ (sAβ) species, such as oligomers, are more neurotoxic than insoluble Aβ (insAβ) plaques, and could potentially serve as biomarkers for pre-symptomatic stages of AD. Therefore, detecting sAβ is a fundamental requirement for early diagnosis of AD and therapy monitoring. Near infrared fluorescence ocular imaging (NIRFOI) has the potential for early preliminary screening of AD. Although imaging technologies such as MRI and PET are very useful for diagnosis of AD, they are too expensive for preliminary screening. In contrast, near infrared fluorescence (NIRF) imaging, due to its low cost, easy operation, high throughput capacity, and straightforward data analysis, is one of the imaging methods with the most potential. However, NIRF brain imaging has nearly no potential for clinical application in AD diagnosis, due to the tissue penetration limitations of NIR light. Nonetheless, the retina/eye can be used as a window to the brain, and NIRF ocular imaging (NIRFOI) is a natural alternative method due to 1) the excellent transparency of eyes, and 2) Aβ pathology in the retinas is correlated with brain Aβ pathology. Our preliminary data indicates that NIRFOI is feasible to detect Aβs in the eyes of mice. Due to its low cost, easy operation, and high sensitivity, we believe that NIRFOI has the clinical potential to detect the early Aβ pathology, and could be used for preliminary screening of AD patients at pre-symptomatic stage in the future. In this application, we propose the concept of NIRFOI, which, to the best of our knowledge, has not been explored. In this proposal, we will validate NIRFOI with our probe CRANAD-102 for detecting sAβ in eyes, and for monitoring the changes of sAβ species during disease progression and drug treatment in AD mice.