Direct Tracking of Amyloid and Tau Dynamics in Neuroblastoma Cells Using Nanoplasmonic Fiber Tip Probes

Abstract

Amyloid plaques and neurofibrillary tangles are the pathological hallmarks of Alzheimer's disease. However, there has been a long-standing discussion on the dynamic relations between A β and tau proteins, partially due to the lack of a tool to track protein dynamics in individual live neurons at the early stage of A β generation and tau phosphorylation. Here, we developed nanoplasmonic fiber tip probe (nFTP) technology to simultaneously monitor A β42 generation and tau phosphorylation (at serine 262) in living, single neuroblastoma cells over 12 h. We observed that A β42 generation, under clinically relevant anesthetic treatment, preceded tau phosphorylation, which then facilitated A β42 generation. This observation is also supported by measuring proteins in cell lysates using the ultrasensitive label-free photonic crystal nanosensors. nFTP therefore provides an advanced method to investigate protein expression and post-translational modification in live cells and determine outcomes of intervention of Alzheimer's disease and other neurodegenerative disorders.

Graphical Abstract