Minimalistic in vitro systems for investigating tau pathology

• Published in: Journal of neuroscience methods 2019-05, Vol.319, p.69-76
• Main Authors: Hallinan, Grace I., Pitera, Aleksandra P., Patel, Prutha, West, Jonathan, Deinhardt, Katrin
• Format: Article
• Language: English
• Subjects: Alzheimer’s disease; Microfluidic devices; Prion-like propagation; Tau; Tauopathy
• ISSN: 0165-0270; 1872-678X
• DOI: 10.1016/j.jneumeth.2018.09.032

•Misfolded tau spreads from cell to cell, and propagates in a prion-like manner.•In vitro and in vivo models exist that recapitulate aspects of tau pathology.•Microfluidic devices can recreate minimalistic, manipulatable neuronal arrays in vitro.•Use of these devices helps advancing our mechanistic understanding of tauopathy. Neurofibrillary tangles, formed of hyperphosphorylated, misfolded tau accumulations, are a pathological hallmark of neurodegenerative diseases such as Alzheimer’s disease (AD) and frontotemporal dementia. The neuroanatomical localisation of tau pathology in AD brains of different disease stages suggests that tau tangle pathology is spreading throughout the brain along connected neuronal circuits. Pathogenic tau can act as a prion-like seed, inducing the misfolding of native tau and leading to disease propagation throughout the brain. However, it is not yet fully understood how tau spreads between individual neurons or brain regions. Here, we review the models for investigating tau propagation in vitro, and summarise the findings from key studies into the mechanisms of tau pathology propagation in disease.