P3‐224: NOVEL FLUORESCENT MOLECULAR PROBES THAT DETECT RETINAL AMYLOID β ASSOCIATED WITH ALZHEIMER'S DISEASE
Year: 2019
Type: article
Abstract: The accumulation and deposition of amyloid deposits in the brain is the hallmark of many neurodegenerative diseases, including Alzheimer's disease (AD). To date, late-stage diagnosis of AD is achieved using functional memory and behavioral tests; however, early stage asymptomatic diagnosis remains a challenge. Imaging using radiolabeled amyloid-targeting agents have made it possible to use positron emission tomography (PET) to image amyloid deposits in the brains of living patients, but there remains a need for more readily available and affordable diagnostic tests. Amydis aims to address this unmet need with our novel fluorescent molecules that detect the biomarker Aβ in the retina, a more accessible part of the CNS than the brain. We have developed a library of fluorescent probes capable of labeling amyloids in the retina, which allows enhanced visualization of amyloids and colorimetric discrimination of the amyloids as a function of their protein composition. To assess whether these novel molecular probes can stain amyloid deposits in the retina and brain, PSAPP transgenic mice were injected intraperitoneally with one of our analogues, AMDX-201. Live retinal imaging and ex vivo immunohistochemistry were used to see colocalization of AMDX-201 with an Aβ sequence specific antibody (6E10). Amydis’ novel probes demonstrated the ability to fluorescently detect Ab deposits in ex vivo human brain and retinal tissues from AD patients. These fluorescent amyloid-binding probes display a significant fluorescence enhancement upon binding with aggregates of Aβ40 and Aβ42 as compared to the free probe in solution. Live retinal imaging and ex vivo immunohistochemistry demonstrated that AMDX-201 colocalized with 6E10. Additionally, we confirmed that our lead compounds were able to stain amyloid deposits from post-mortem brain tissues from AD and cerebral amyloid angiopathy (CAA) patients. Moreover, positive staining of these probes completely colocalized with 6E10 positive staining in CAA-laden plaques. In our preliminary experiments of post-mortem retinal tissue of humans with confirmed AD, 6E10 staining was completely colocalized with Thioflavin S positive aggregates. Amydis’ novel fluorescent compounds creates a novel opportunity to identify retinal amyloid accumulation associated with AD and CAA. These probes also have potential utility for detecting amyloid biomarkers in other neurodegenerative diseases.
Source: Alzheimer s & Dementia
Authors: Suhail Rasool, Lyndsay M. Randolph, Jennifer Ngolab, Kevin Cao, Richard D'Souza, Jerry Yang, Stella Sarraf, Robert A. Rissman
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2981098294