Tauopathies with parkinsonism: clinical spectrum, neuropathologic basis, biological markers, and treatment options.
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.
Ludolph
A C
AC
Department of Neurology, University of Ulm, Ulm, Germany. albert.ludolph@rku.de
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Saint-Raymond
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van Swieten
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MT
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D000818:Animals; D015415:Biomarkers; D003704:Dementia / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D015195:Drug Design; D005843:Geography; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008954:Models, Biological; D009154:Mutation; D052556:Niemann-Pick Disease, Type C / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology; D010301:Parkinson Disease, Postencephalitic / Q000150:complications / Q000503:physiopathology; D020734:Parkinsonian Disorders / Q000150:complications* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D020774:Pick Disease of the Brain / Q000150:complications / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D013494:Supranuclear Palsy, Progressive / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology; D024801:Tauopathies / Q000150:complications* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D016875:tau Proteins / Q000235:genetics
D015415:Biomarkers; C054369:MAPT protein, human; D016875:tau Proteins; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases