Influence of tau on neuronal traffic mechanisms

Summary

One of the earliest changes in the brains of Alzheimer’s disease (AD) patients is the loss of synapses, concomitant with the abnormal phosphorylation of tau protein and its redistribution into the somatodendritic compartment that is one of the hallmarks of AD. Tau’s major physiological function is to stabilize axonal microtubules for their role as tracks for the transport of vesicles and organelles, suggesting that the abnormal changes in tau could be related to the loss of synapses and neuronal degeneration. Experiments with cell models show that tau can indeed act as an inhibitor of transport in neurons, particularly in the anterograde direction. The result is that cell processes of neurons become starved of their nutrients, leading to the decay of synapses followed by the loss of axons and dendrites. In particular, tau can also interfere with the transport of APP, which therefore may offer a link between the two proteins causing abnormal protein aggregates in AD.