Experimental study demonstrates activity-dependent physiological release of endogenous tau in mature cortical neurons, suggesting a mechanism for trans-synaptic pathological spread.
Key Points
To determine whether physiological neuronal activity stimulates the secretion of endogenous tau from healthy cortical neurons and identify the underlying cellular mechanism.
Stimulated neuronal activity and activated AMPA receptors in healthy, mature cortical neurons to measure endogenous tau release.
Assessed extracellular versus intracellular tau phosphorylation states and calcium dependency during release.
Blocked pre-synaptic vesicle release using tetanus toxin and inhibited action potentials using tetrodotoxin to evaluate secretory pathways.
Stimulation of neuronal activity or AMPA receptor activation induced calcium-dependent release of endogenous tau with reduced phosphorylation relative to intracellular tau.
Pre-synaptic vesicle blockade by tetanus toxin and neuronal inhibition by tetrodotoxin both significantly impaired AMPA-mediated tau release.