A Novel Impedimetric Based Screening System for Label-Free Detection of Tau Hyperphosphorylation in Human Cells

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disease that affects more than 4 million people in Europe. AD is a member of a group of neurological disorders collectively referred as tauopathies, which are char acterized by the aggregation of hyperphosphorylated tau lead ing to neuronal cytotoxicity and cognitive impairments. Given the complex pathological mechanism, drug development pro grams for AD rely heavily on animal models, making research very expensive and time-consuming. In this context the lack of fast, label-free and high throughput/high content screening capable cell-based assays is a bottleneck in today’s active pharmaceutical ingredient development. To improve the identification, optimization and validation during the high-cost Hit-to-Lead cycle of AD drugs we report for the first time on an in vitro AD model, where pathological consequences of induced hyperphosphorylation can be detected quantitatively and label-free by microelectrode array based impedance spec troscopy. Our findings provide a novel real-time recording technique for testing the efficiency of tau kinase inhibitors or other lead structures directed to tau hyperphosphorylation on differentiated SH-SY5Y cells.