Near infrared Fluorescence Ocular Imaging of Soluble Amyloid Beta Species

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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.