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

European Journal of Neurology - Tập 16 Số 3 - Trang 297-309 - 2009
Albert C. Ludolph1, Jan Kassubek1, G. Bernhard Landwehrmeyer1, E. Mandelkow2, Eva‐Maria Mandelkow2, David J. Burn3, D Caparros-Lefèbvre4, Kirk A. Frey5, Justo Garcı́a de Yébenes6, Thomas Gasser7, Peter Heutink8, Günter U. Höglinger9, Zygmunt Jamrozik10, K. A. Jellinger11, A Kazantsev12, Hans Kretzschmar13, Anthony E. Lang14, Irene Litvan15, José J. Lucas16, Patrick L. McGeer17, Stacey Melquist18, Wolfgang H. Oertel9, Markus Otto1, Dominic C. Paviour19, T. Reum20, Agnès Saint-Raymond21, John C. Steele22, Markus Tolnay23, Hayrettin Tumani1, John C. van Swieten24, M T Vanier25, Jean‐Paul Vonsattel26, Steven L. Wagner27, Zbigniew K. Wszołek28
1Department of Neurology, University of Ulm, Ulm, Germany
2Max Planck Unit for Structural Molecular Biology, c/o DESY, Notkestr, Hamburg, Germany
3Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, UK
4Centre Hospitalier de Valenciennes, Résidence du Val d'Escaut, Avenue Desandrouin, Valenciennes, France
5University of Michigan Medical Center, 1500 E Medical Center Dr, Ann Arbor, MI, USA
6Hospital Ramon y Cajal, Neurology, Carretera Colmenar, Madrid, Spain
7Universitätsklinikum Tübingen, Zentrum für Neurologie, Hoppe-Seyler-Strasse, Tübingen, Germany
8VU University Medical Center, Department of Clinical Genetics and Anthropogenet, van der Boechorststraat, Amsterdam, the Netherlands
9Philipps-Universität, Neurologie, Rudolf-Bultmann-Strasse, Marburg, Germany
10Medical University of Warsaw, Neurology, Banacha, Warsaw, Poland
11Institute of Clinical Neurobiology, Kenyongasse, Vienna, Austria
12Massachusetts General Hospital, MIND/Harvard Medical School, Charlestown, MA, USA
13Institut für Neuropathologie, BrainNet (German Brain Bank), Feodor-Lynen-Strasse, Munich, Germany
14Toronto Western Hospital, Movement Disorders Center, Toronto, ON, Canada
15University of Louisville, School of Medicine/Department of Neurology, Louisville, KY, USA
16Centro de Biologica Molecular "Severo Ochoa," Universidad Autonoma de Madrid and CiberNed, Cantoblanco, Madrid, Spain
17University of British Columbia, Kinsmen Laboratory of Neurological Research, Vancouver, BC, Canada
18Mayo Clinic, Department of Neuroscience, Jacksonville, FL, USA
19National Hospital for Neurology, Dementia Research Centre, London, England
20Bundesinstitut für Arzneimittel & Medizinprodukte, Wissenschaftlicher Service/Klinische Prüfungen, Georg-Kiesinger-Allee, Bonn, Germany
21European Medicines Agency (EMEA), Scientific Advice and Orphan Drugs Sector, 7 Westferry Circus, Canary Wharf, London, England
22Guam Memorial Hospital, Neurology, Carlos Camacho Way, Tamuning, Guam
23Institut für Pathologie, Schönbeinstrasse, Basel, Switzerland
24University Hospital Rotterdam, Department of Neurology, Erasmus MC, Dr Molewaterplein, GD Rotterdam, the Netherlands
25Institut National de la Santé et de la Recherche Médicale, Unit 820, Laënnec Medical School, Lyon, France
26New York Brain Bank, Columbia University, Pathology, Babies Hospital, New York, NY, USA
27Deutsche PSP-Gesellschaft e.V. (PSP Germany), c/o S. Wagner, Könneritzstrasse, Leipzig, Germany
28Mayo Clinic, Department of Neurology, Jacksonville, FL, USA

Tóm tắt

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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European Journal of Neurology

Tập 16 Số 3

297-309

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