Tauopathies

Filamentous tau inclusions in neurons and glial cells of the brain are the pathological hallmark of a number of neurodegenerative disorders (designated “tauopathies”) clinically characterized by dementia or parkinsonism. Alzheimer’s disease (AD) is the most common tauopathy, and is characterized by neurofibrillary tangles and the deposition of b-amyloid in senile plaques. Neurofibrillary tangles in AD consist predominantly of paired helical filaments and contain all six isoforms of hyperphosphorylated tau (1-3). Other tauopathies such as progressive supranuclear palsy, corticobasal degeneration, Pick’s disease, and argyrophilic grain disease show tau pathology in the absence of senile plaques, and are pathologically distinguished from each other by different types and distribution of tau-positive inclusions in the brain. The etiological role of the tau protein in neurodegeneration has been questioned for a long time, but has been convincingly demonstrated by the identification of mutations in the tau gene in a number of familial disorders with dementia and/or parkinsonism (4-6). All disorders with mutations in the tau gene show accumulation of abundant filamentous tau protein in the brain.