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

Department of Neurology, University of Ulm, Ulm, Germany.
European Journal of Neurology (Impact Factor: 4.06). 04/2009; 16(3):297-309. DOI: 10.1111/j.1468-1331.2008.02513.x
Source: PubMed


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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Available from: Zygmunt Jamrozik
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    • "Progressive supranuclear palsy (PSP) is characterized by Parkinsonism associated with signs like supranuclear gaze palsy, early falls, dysphagia, dysarthria, axially pronounced rigidity, and behavioral/cognitive impairment [71]. PSP can be subdivided into different subtypes that are characterized by their clinical course, most probably related to different patterns of pathological tau distribution in the brain. "
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    • "Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease that causes the gradual deterioration and death of specific volumes of the brain (Richardson et al., 1963; Steele et al., 1964). Ludolph and colleagues showed that the neuropathologic features of PSP include marked midbrain atrophy and atrophy of the pallidum, thalamus, subthalamic nucleus, and frontal lobes (Ludolph et al., 2009). Clinical criteria for the diagnosis of PSP are: a gradually progressive disorder, an onset at the age of 40 years or later, a presence of vertical supranuclear palsy, a slowing of vertical saccades and a postural instability with falls in the first year of disease onset. "
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    • "Its etiology is unknown. From a pathological point of view, the disease consists in a neurodegenerative process that involves the basal ganglia, the brainstem, the prefrontal cortex and the cerebellum, with accumulation of a tau protein - hence the classification as tauopathy [3]. Onset typically occurs after 40 years of age. "
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