Tauopathies with parkinsonism: clinical spectrum, neuropathologic basis, biological markers, and treatment options

Authors


Prof Dr Albert C. Ludolph, Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany (tel.: +49 731 1771200; fax: +49 731 1771202; e-mail: albert.ludolph@rku.de.).

Abstract

Tauopathies with parkinsonism represent a spectrum of disease entities unified by the pathologic accumulation of hyperphosphorylated tau protein fragments within the central nervous system. These pathologic characteristics suggest shared pathogenetic pathways and possible molecular targets for disease-modifying therapeutic interventions. Natural history studies, for instance, in progressive supranuclear palsy, frontotemporal dementia with parkinsonism linked to chromosome 17, corticobasal degeneration, and Niemann-Pick disease type C as well as in amyotrophic lateral sclerosis/Parkinson–dementia complex permit clinical characterization of the disease phenotypes and are crucial to the development and validation of biological markers for differential diagnostics and disease monitoring, for example, by use of neuroimaging or proteomic approaches. The wide pathologic and clinical spectrum of the tauopathies with parkinsonism is reviewed in this article, and perspectives on future advances in the understanding of the pathogenesis are given, together with potential therapeutic strategies.

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