ABSTRACT
Tau belongs to the family of microtubule-associated proteins (MAP) with a central role in the assembly of tubulin monomers into microtubules to constitute the microtubule network (1-3). Tau is highly expressed in the axons of mature and growing neurons, although low levels are also present in oligodendrocytes and astrocytes (4,5). In non-neuronal cells, tau can be detected in several peripheral tissues such as heart, kidney, lung, muscle, pancreas, and testis (6-8). In addition to the polymerization and stabilization of microtubules, neuronal tau is important for morphogenesis, axonal extension, and the regulation of motor protein-mediated transport of vesicles and organelles along the microtubules (9-11). In human brain, six different tau isoforms are generated by alternative splicing from a single unique gene, MAPT, located over a 140 kb region on the long arm of chromosome 17 (12). Alternative splicing is an important mechanism, generating different protein isoforms from a single gene, which occurs in about 60% of all human genes (13,14). It is expected that the diverse tau isoforms produced in human brain each have specific physiological roles since they are differentially expressed during development and may be differentially distributed in neuronal subpopulations (15-17).
