Phylogenetic diversity of the expression of the microtubule-associated protein tau: implications for neurodegenerative disorders

The microtubule-associated protein tan regulates the dynamic stability of t he neuronal cytoskeleton by interacting with microtubules. It is encoded by a single gene, but expressed in a Variety of isoforms due to differential RNA splicing. Six isoforms can be found in the human central nervous system . These isoforms differ in their ability to promote the assembly of microtu bules as well as in their capacity to stabilize existing microtubule struct ures. Furthermore, some of the isoforms of tau are specifically involved in the pathogenesis of neurodegenerative disorders. Thus, splicing of tau mig ht critically influence the physiological functions of tau protein as well as the pathogenesis of neurodegenerative diseases with tauopathy. The prese nt study addresses the differential expression of the six isoforms of tau i n the central nervous system of 12 mammalian species including Homo sapiens . The occurrence of each of the six tau isoforms was highly variable. Howev er, species that were phylogenetically related expressed a similar pattern of tau isoforms. These results suggest a phylogenetic descent of splicing p aradigms, which can be matched with known phylogenetic concepts based on mo rphological and molecular genetical studies. Especially, the unique express ion pattern of tan isoforms in the human central nervous system implicates a possible Link to the particular vulnerability of humans to neurodegenerat ive disorders with tauopathy, namely Alzheimer's disease, frontotemporal de mentia and Pick's disease. (C) 1999 Elsevier Science B.V. All rights reserv ed.