Four-Repeat Tauopathies: Current Management and Future Treatments

Neurotherapeutics. 2020 Oct;17(4):1563-1581. doi: 10.1007/s13311-020-00888-5.


Four-repeat tauopathies are a neurodegenerative disease characterized by brain parenchymal accumulation of a specific isoform of the protein tau, which gives rise to a wide breadth of clinical syndromes encompassing diverse symptomatology, with the most common syndromes being progressive supranuclear palsy-Richardson's and corticobasal syndrome. Despite the lack of effective disease-modifying therapies, targeted treatment of symptoms can improve quality of life for patients with 4-repeat tauopathies. However, managing these symptoms can be a daunting task, even for those familiar with the diseases, as they span motor, sensory, cognitive, affective, autonomic, and behavioral domains. This review describes current approaches to symptomatic management of common clinical symptoms in 4-repeat tauopathies with a focus on practical patient management, including pharmacologic and nonpharmacologic strategies, and concludes with a discussion of the history and future of disease-modifying therapeutics and clinical trials in this population.

Keywords: 4R-tauopathy (4R-tau); Richardson’s syndrome (PSP-RS); atypical parkinsonism; corticobasal degeneration (CBD); corticobasal syndrome (CBS); progressive supranuclear palsy (PSP).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Clinical Trials as Topic / methods
  • Disease Management*
  • Forecasting
  • Humans
  • Motor Disorders / diagnosis*
  • Motor Disorders / genetics
  • Motor Disorders / therapy*
  • Tauopathies / diagnosis*
  • Tauopathies / genetics
  • Tauopathies / therapy*
  • Treatment Outcome