Visualizing Tau protein neurofibrillary tangles in hiPS28 retinal neurons and postmortem samples of AD patient’s retina using BODIPY-based fluorescent ligand

Background: Alzheimer’s disease (AD) is a neurodegenerative disease characterized by the progressive impairment of behavioral and cognitive functions. Neurofibrillary tangles (NFTs), composed of hyperphosphorylated tau protein, are established hall-marks of the pathology and Alzheimer’s disease progression. Developing a therapeutic strategy based on the selective detection of NFTs in the retina is a promising diagnostic tool for early detection of AD. In this study we describe development of highly specific tau fluorophores, such as BT-1, for selective detection of pathological forms of tau protein and the use of cell permeant peptides (CPP) nanocage to deliver BT-1 to hiPSC-derived retinal neurons and in and postmortem samples of AD patients’ retina. Methods: BT-1 fluorophore (Soloperto et al., 2021) is a BODIPY-based fluorescent probe developed to bind hyperphorylated and oligomeric tau. The fluorescent probe BT-1 was delivered to retinal cells and in retinal tissues using CCP, natural nanocages capable of encapsulating small molecules. Results: Nanocage-BT-1 complex has been effectively internalized, binding hyperphosphorylated and oligomeric tau in iPSC derived retinal cells and AD retinal slices. Conclusion: We demonstrated the ability of CPP nanocages loaded with the fluorescent probe BT-1 to detect NFTs in iPSC derived retinal cells and AD retinal slices developed a potential method for the early diagnosis of AD.