Neuronal activity enhances tau propagation and tau pathology in vivo

Extracellular Tau Oligomers Induce Disruption of Endogenous Tau Distribution, Invasion of Tau into the Somatodendritic Compartment and Axonal Transport Dysfunction

“…It is encouraging to think that the isoform effects seen in these experiments are similar to those observed with different tau "seeds", tau aggregates of varying morphologies isolated from cells that reproduce these differing morphologies upon exposure to tau-expressing cells [221,223,228]. It is known that different isoforms of tau exhibit differing propensities for aggregation [166,273,274] and given that each isoform was exposed to AA for an equal time period prior to UV exposure, it is possible that each isoform oligomerized to its own unique degree within an incubation period of constant length.…”

“…While little mechanistic evidence exits, several hypotheses have been proposed as to how this takes place. Tau has been demonstrated to be released at the synapse during neuronal activity [228]. Tau may also be released through exocytosis at the cell body or synapse, or from exosomes derived from multivesicular bodies [229,230].…”

Transmission of Tau Pathology from Human to Rodent Brain: How to Humanise Animal Models for Alzheimer’s Disease Research

“…Recently, it was shown that synaptic terminals release tau upon depolarisation, however, the levels of released tau were higher in synaptic terminals from AD brains [91,92]. Calafate et al [92] demonstrated that hippocampal neurons expressing human truncated tau K18 (aaQ244-E372) with the P301L mutation develop intracellular tau aggregates on exposure to K18P301L fibrils aggregated with synthetic heparin.…”

“…The depolarisation of synaptic terminals from AD brains is enhanced in comparison to control human synapses. Moreover, AD synaptic terminals contain tau oligomers [94], C-terminally truncated tau along with 20 kDa tau fragment [91], which may be released after activation. In addition, tau is reported as a key component of tunnelling nanotubes (TNT) which are tubular structures that facilitate cell-cell communication under stress [95].…”

Synaptic Function and Dysfunction in Alzheimer’s Disease

“…Concerning tau, its release can be stimulated by enhanced neuronal activity; Wu et al [112] showed that increasing neuronal activity enhances release and transfer of tau in vitro and exacerbate tau pathology in vivo. As neurons within the AD brain can be hyperactive [106], thus enhanced neuronal activity may increase tau pathology.…”