Tau mislocalization to dendritic spines is a common mechanism in neurodegenerative diseases including AD and PD

Progressively more research suggests that diverse neurodegenerative diseases including Alzheimer’s disease (AD) and Parkinson’s disease (PD) share common pathological hallmarks and cellular mechanisms. One such mechanism involves the redistribution of microtubule associated protein tau (MAPT) from the axon into the somatodendritic compartments of neurons, leading to loss of tau polarity. Under normal physiological conditions, the distribution of tau proteins is polar. Tau is enriched in axons and has low presence in postsynaptic structures including the soma, dendrites and dendritic spines. In our recent studies, we found that the tau polarity is lost or reversed in neurodegenerative diseases. The loss of polarity is followed by mislocalization of tau into dendritic spines, the postsynaptic structures found in most excitatory glutamatergic synapses, and subsequent postsynaptic deficits and cognitive impairments. The clarification of the signaling steps that lead to tau-mediated synaptic deficits and cognitive impairments will shed new mechanistic insight on the pathogenesis of AD and PD. It may also uncover novel drug targets for treating and preventing these diseases.  The combination of live imaging technique and spintronic technology will allow us to longitudinally monitor tau trafficking and electrophysiological activities at multiple time points and will be a powerful tool for mechanistic studies of tau mislocalization.