Neurofibrillary Degeneration in Progressive Supranuclear Palsy and Corticobasal Degeneration

TLDR

Tau protein aggregates form disease‑specific neuronal inclusions, with distinct isoform patterns in Alzheimer’s, Pick’s disease, and other tauopathies, indicating that clinical phenotypes are linked to specific tau isoforms and supported by familial frontotemporal dementia mutations. The study aims to show that progressive supranuclear palsy and corticobasal degeneration constitute a third tauopathy group distinguished by intraneuronal inclusions of exon‑10‑containing tau isoforms. The authors used isoform‑specific antibodies with one‑ and two‑dimensional gel electrophoresis and western blotting to analyze tau inclusions. Exon‑10‑containing tau isoforms distinguish PSP/CBD from AD and PiD, confirming a third distinct tauopathy group.

Abstract

Abstract : Pathological tau prroteins that constitute the basic matrix of neuronal inclusions observed in numerous neurodegenerative disorders are disease specific. This is mainly the consequence of the aggregation of specific sets of tau isoforms according to the diseases, i.e., six isoforms in Alzheimer's disease (AD) and exclusively the three tau isoforms lacking the corresponding sequence of exon 10 (E10‐) in Pick's disease (PiD). By using antibodies specific to the different tau isoforms and one‐ and two‐dimensional gel electrophoresis followed by western blots, we demonstrate herein a third group of neurodegenerative disorders characterized by intraneuronal inclusions exclusively constituted of tau isoforms containing the sequence corresponding to exon 10, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Together, tau isoforms with exon 10 clearly differentiate three groups of neurodegenerative diseases : AD, PiD, and PSP/CBD. For each group, the neuropathological nd clinical phenotypes are most likely related to specifric sets of tau isoforms expressed by the vulnerable neuronal populations. The recently described mutations of the tau gene responsible for familial frontotemporal dementias also support this hypothesis.