Minimalistic in vitro systems for investigating tau pathology.

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.