The tauopathies

Tauopathies are a clinically and neuropathologically heterogeneous group of neurodegenerative disorders, characterized by abnormal tau aggregates. Tau, a microtubule-associated protein, is important for cytoskeletal structure and intracellular transport. Aberrant posttranslational modification of tau results in abnormal tau aggregates causing neurodegeneration. Tauopathies may be primary, or secondary, where a second protein, such as Aß, is necessary for pathology, for example, in Alzheimer's disease, the most common tauopathy. Primary tauopathies are classified based on tau isoform and cell types where pathology predominates. Primary tauopathies include Pick disease, corticobasal degeneration, progressive supranuclear palsy, and argyrophilic grain disease. Environmental tauopathies include chronic traumatic encephalopathy and geographically isolated tauopathies such as the Guam-Parkinsonian-dementia complex. The clinical presentation of tauopathies varies based on the brain areas affected, generally presenting with a combination of cognitive and motor symptoms either earlier or later in the disease course. As symptoms overlap and tauopathies such as Alzheimer's disease and argyrophilic grain disease often coexist, accurate clinical diagnosis is challenging when biomarkers are unavailable. Available treatments target cognitive, motor, and behavioral symptoms. Disease-modifying therapies have been the focus of drug development, particularly agents targeting Aß and tau pathology in Alzheimer's disease, although most of these trials have failed.