Tau filaments in neurodegenerative diseases.

The ordered assembly of Tau protein into abnormal filamentous inclusions is a defining characteristic of many human neurodegenerative diseases. Thirty years ago, we reported that Tau is an integral component of the intraneuronal filaments of Alzheimer's disease. All six brain Tau isoforms make up those filaments. Twenty years ago, we and others showed that mutations in MAPT, the Tau gene, cause familial forms of frontotemporal dementia, thus proving that dysfunction of Tau protein is sufficient to cause neurodegeneration and dementia. More recently, we showed that high-resolution structures of Tau filaments from human brain can be determined by electron cryo-microscopy. These filaments may form the seeds that underlie the prion-like properties of aggregated tau.