Microtubules and the Protein Tau

The protein tau is central to the pathological process underlying sporadic AD. It is chiefly a neuronal protein and is produced in all portions of the nervous system (CNS, PNS, ENS) (Trojanowski et al. 1989). In immature nerve cells, tau is distributed diffusely throughout the entire cell, but during cell maturation it converts into a primarily axonal protein. Tau is born in the cell soma’s rough endoplasmatic reticulum, it clears all cellular checkpoints for quality control, and, in this fully functional state, is then transferred to the axonal compartment (Lee et al. 2001; Scholz and Mandelkow 2014). In healthy nerve cells, the protein promotes self-assembly of axonal microtubules and stabilizes them (Fig. 4.1a). Together with motor proteins, microtubules are required for anterograde and retrograde transport of substances within the axon. To a lesser extent, the protein is also present in neuronal somata, dendritic processes, astrocytes, and oligodendrocytes. However, in contrast to the situation in axons, the microtubules in the somatodendritic compartment are mainly stabilized by other microtubule-associated proteins (Mandelkow and Mandelkow 1998, 2012; Binder et al. 2004; von Bergen et al. 2005; Avila 2006; Goedert et al. 2006; Alonso et al. 2008; Iqbal et al. 2009).