Neurofibrillary degeneration in progressive supranuclear palsy and corticobasal degeneration: Tau pathologies with exclusively "exon 10" isoforms

Pathological tau proteins that constitute the basic matrix of neuronal incl usions observed in numerous neurodegenerative disorders are disease specifi c. This is mainly the consequence of the aggregation of specific sets of ta u isoforms according to the diseases, i.e., six isoforms in Alzheimer's dis ease (AD) and exclusively the three tau isoforms lacking the corresponding sequence of exon 10 (E10-) in Pick's disease (PID). By using antibodies spe cific to the different tau isoforms and one- and two-dimensional gel electr ophoresis followed by western blots, we demonstrate herein a third group of neurodegenerative disorders characterized by intraneuronal inclusions excl usively constituted of tau isoforms containing the sequence corresponding t o exon 10, progressive supranuclear palsy (PSP) and corticobasal degenerati on (CBD), Together, tau isoforms with exon 10 clearly differentiate three g roups of neurodegenerative diseases: AD, PID, and PSP/CBD, For each group, the neuropathological and clinical phenotypes are most likely related to sp ecific sets of tau isoforms expressed by the vulnerable neuronal population s. The recently described mutations of the tau gene responsible for familia l frontotemporal dementias also support this hypothesis.