CANCELLED - Tau Protein and Neurodegeneration Event

Abundant inclusions made of hyperphosphorylated filamentous tau protein are characteristic of many human neurodegenerative diseases, including Alzheimer’s disease, tangle-only dementia, chronic traumatic encephalopathy, Pick’s disease, argyrophilic grain disease, progressive supranuclear palsy, corticobasal degeneration, as well as dominantly inherited frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17T). The identification of mutations in MAPT, the tau gene, in FTDP- 17T established that dysfunction of tau protein is sufficient to cause neurodegeneration and dementia. Tau inclusions appear to exist as multiple conformers that propagate through the brain, suggesting a conceptual link between tauopathies and prion diseases. The structures of amyloid filaments can be determined using electron cryo-microscopy. We have reported the structures of tau filaments from Alzheimer’s disease, Pick’s disease, chronic traumatic encephalopathy and corticobasal degeneration. Evidence so far indicates inter-disease, but not inter-subject, variability of tau filament structures.

Different tau isoforms play a role in giving rise to distinct filament structures. In addition, cofactors and/or post-translational modifications may be involved. It seems clear that filamentous tau adopts distinct folds in different human neurodegenerative diseases, establishing the existence of conformers of assembled tau.