Modulation of the spread of pathological tau in vitro and in vivo

In tauopathies such as Alzheimer’s disease, tau aggregates are known to propagate across functionally connected neuronal networks, but the mechanisms underlying this process are poorly understood. Several lines of evidence support the hypothesis that tau release is dependent on neuronal activity. Pathological tau can be found in the extracellular space, inside synaptic vesicles, and other synaptic compartments, or in a free form. We aim to test both in vitro and in vivo the effect of selected botulinum neurotoxins (BoNTs) and tetanus neurotoxin (TeNT) on the release of tau from synaptic terminals. BoNTs and TeNT enter synapses and cleave different synaptic SNARE proteins, impairing synaptic vesicle fusion and release and they may affect tau spread.