TAU SECRETION AND PROPAGATION

Abstract

One of the neuropathological hallmarks of AD is an increase in the intracellular amount of tau. In order to revert that increase, one mechanism used by cells could be the secretion of tau to the extracellular space. It has been postulated that under physiological conditions, an increase in the intracellular amount of tau facilitates its secretion to the extracellular space. Extracellular tau can be toxic and can propagate through its interaction with neuronal or glia cells. In this presentation we will comment on: a) the regions of tau molecule that could be involved in the protein secretion when it is in monomeric form. Those tau regions could be different to those needed for the secretion of truncated or aggregated tau; b) some mechanisms for the interaction of extracellular tau with neuronal and microglia cells. a) COS-7 cell line was used as an in vitro model. Cells were transfected with different tau constructs. Purified tau was added to primary neuron or microglia cultures to study the interaction between tau and these cell types a) N-terminal region of tau molecule could be required for the secretion of soluble intracellular tau. b) Extracellular monomeric tau could react with specific cell receptors present in neurons or in microglia cells A possible mechanism for monomeric tau secretion and further interactions of tau with neuron or microglia cells is proposed.