Resources
Authors & Affiliations
Ylenia Gigante
Abstract
Alzheimer's disease (AD) is a tauopathy characterized by memory loss and cognitive decline. Tau protein plays a crucial role in the assembly and stabilization of microtubules. In disease conditions, aggregates of misfolded and hyperphosphorylated tau protein leads to neurofibrillary tangles. AD associated neurodegenerative changes in the brain are accompanied by structural of the retina, such as, optic nerve degeneration and reduced thickness of retinal layers. Numerous studies have shown the presence of tau aggregates in both AD mouse models and postmortem samples of AD patients’ retina. The quantitative detection of pathological tau is very promising from a clinical point of view. To this purpose, has been designed a highly specific tau fluorophore, BT-1. In this project, we delivered a tau-specific fluorophore, BT-1, into living human retinal cells through nanocages and tested the ability of BT-1 to detect Neurofibrillary Tangles on iPSC derived retinal cells and postmortem samples of AD patients’ retina.Method: The delivery of BT-1 into living cells was achieved by humanized ferritin nanocages.Results: The fluorophore BT-1 has been effectively delivered within living retinal cells binding phosphorylated and oligomeric tau; Moreover, detected the pathological forms of tau protein in fixed retinal cells and in and postmortem samples of AD patients’ retina.Conclusion: We demonstrated the ability of the fluorescent probe BT-1 to detect NFTs in both living and fixed iPSC derived retinal cells, and in AD retina slice. BT-1 can be used to monitor tau fibrils in retinal tissue as potential tool for the investigation of tauopathies.