Novel BODIPY-based sensor for selective detection of misfolded Tau protein in retinal and cortical iPSC derived models for Frontotemporal Dementia

Tauopathies, such as frontotemporal dementia (FTD) and Alzheimer’s diseases, are character- ized by the hyperphosphorylation and accumulation of the microtubule-associated protein Tau in the human brain, leading to a synaptic and neuronal loss. Numerous studies have shown a strong correlation between the number of neurofibrillary tangles of the Tau protein and Alzheim- er’s disease progression, making the quantitative detection of tau very promising from a clinical point of view. To investigate the complex Tau aggregation, it is beneficial to use fluorescence sensors that enable to detect and quantify pathological Tau aggregates. Here we describe the characterization of a fluorescent probe, consisting of a BODIPY core (BT1), with excellent pho- tophysical properties and high selectivity. BT1 was tested onto human control and FTD iPSCs derived retinal and cortical neurons showing good affinity for hyperphosphorylated Tau protein filaments with minimal background noise.