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

Identifieur interne : 002103 ( Main/Merge ); précédent : 002102; suivant : 002104

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

Auteurs : A. C. Ludolph [Allemagne] ; J. Kassubek [Allemagne] ; B. G. Landwehrmeyer [Allemagne] ; E. Mandelkow [Allemagne] ; E. Mandelkow [Allemagne] ; D. J. Burn [Royaume-Uni] ; D. Caparros-Lefebvre [France] ; K. A. Frey [États-Unis] ; J. G. De Yebenes [Espagne] ; T. Gasser [Allemagne] ; P. Heutink [Pays-Bas] ; G. Höglinger [Allemagne] ; Z. Jamrozik [Pologne] ; K. A. Jellinger [Autriche] ; A. Kazantsev [États-Unis] ; H. Kretzschmar [Allemagne] ; A. E. Lang [Canada] ; I. Litvan [États-Unis] ; J. J. Lucas [Espagne] ; P. L. Mcgeer [Canada] ; S. Melquist [États-Unis] ; W. Oertel [Allemagne] ; M. Otto [Allemagne] ; D. Paviour [Royaume-Uni] ; T. Reum [Allemagne] ; A. Saint-Raymond [Royaume-Uni] ; J. C. Steele ; M. Tolnay [Suisse] ; H. Tumani [Allemagne] ; J. C. Van Swieten [Pays-Bas] ; M. T. Vanier [France] ; J. Vonsattel [États-Unis] ; S. Wagner [Allemagne] ; Z. K. Wszolek [États-Unis]

Source :

RBID : ISTEX:46DA66675464C537825E2DA84B0B1D58DE536F61

English descriptors

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.

Url:
DOI: 10.1111/j.1468-1331.2008.02513.x

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ISTEX:46DA66675464C537825E2DA84B0B1D58DE536F61

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<term>Parkinson disease</term>
<term>corticobasal degeneration</term>
<term>frontotemporal dementia with parkinsonism linked to chromosome 17</term>
<term>microtubule‐associated protein tau</term>
<term>multiple system atrophy</term>
<term>parkinsonism</term>
<term>progressive supranuclear palsy</term>
<term>tauopathies</term>
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<div type="abstract" xml:lang="en">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.</div>
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<name sortKey="Kretzschmar, H" sort="Kretzschmar, H" uniqKey="Kretzschmar H" first="H." last="Kretzschmar">H. Kretzschmar</name>
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<wicri:regionArea>Institut für Neuropathologie, BrainNet (German Brain Bank), Feodor‐Lynen‐Strasse, Munich</wicri:regionArea>
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<region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
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</affiliation>
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<name sortKey="Lang, A E" sort="Lang, A E" uniqKey="Lang A" first="A. E." last="Lang">A. E. Lang</name>
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<country xml:lang="fr">Canada</country>
<wicri:regionArea>Toronto Western Hospital, Movement Disorders Center, Toronto, ON</wicri:regionArea>
<wicri:noRegion>ON</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Litvan, I" sort="Litvan, I" uniqKey="Litvan I" first="I." last="Litvan">I. Litvan</name>
<affiliation wicri:level="2">
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>University of Louisville, School of Medicine/Department of Neurology, Louisville, KY</wicri:regionArea>
<placeName>
<region type="state">Kentucky</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Lucas, J J" sort="Lucas, J J" uniqKey="Lucas J" first="J. J." last="Lucas">J. J. Lucas</name>
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<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Centro de Biologica Molecular “Severo Ochoa,” Universidad Autonoma de Madrid and CiberNed, Cantoblanco, Madrid</wicri:regionArea>
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<settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
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<name sortKey="Mcgeer, P L" sort="Mcgeer, P L" uniqKey="Mcgeer P" first="P. L." last="Mcgeer">P. L. Mcgeer</name>
<affiliation wicri:level="1">
<country xml:lang="fr">Canada</country>
<wicri:regionArea>University of British Columbia, Kinsmen Laboratory of Neurological Research, Vancouver, BC</wicri:regionArea>
<wicri:noRegion>BC</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Melquist, S" sort="Melquist, S" uniqKey="Melquist S" first="S." last="Melquist">S. Melquist</name>
<affiliation wicri:level="2">
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Mayo Clinic, Department of Neuroscience, Jacksonville, FL</wicri:regionArea>
<placeName>
<region type="state">Floride</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Oertel, W" sort="Oertel, W" uniqKey="Oertel W" first="W." last="Oertel">W. Oertel</name>
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<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Philipps‐Universität, Neurologie, Rudolf‐Bultmann‐Strasse, Marburg</wicri:regionArea>
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<region type="land" nuts="1">Hesse (Land)</region>
<region type="district" nuts="2">District de Giessen</region>
<settlement type="city">Marbourg</settlement>
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<name sortKey="Otto, M" sort="Otto, M" uniqKey="Otto M" first="M." last="Otto">M. Otto</name>
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<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Neurology, University of Ulm, Ulm</wicri:regionArea>
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<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Tübingen</region>
<settlement type="city">Ulm</settlement>
<settlement type="city">Ulm</settlement>
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<orgName type="university">Université d'Ulm</orgName>
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<name sortKey="Paviour, D" sort="Paviour, D" uniqKey="Paviour D" first="D." last="Paviour">D. Paviour</name>
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<country>Royaume-Uni</country>
<placeName>
<region type="country">Angleterre</region>
</placeName>
<wicri:cityArea>National Hospital for Neurology, Dementia Research Centre, London</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Reum, T" sort="Reum, T" uniqKey="Reum T" first="T." last="Reum">T. Reum</name>
<affiliation wicri:level="3">
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Bundesinstitut für Arzneimittel & Medizinprodukte, Wissenschaftlicher Service/Klinische Prüfungen, Georg‐Kiesinger‐Allee, Bonn</wicri:regionArea>
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<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
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<name sortKey="Saint Aymond, A" sort="Saint Aymond, A" uniqKey="Saint Aymond A" first="A." last="Saint-Raymond">A. Saint-Raymond</name>
<affiliation wicri:level="2">
<country>Royaume-Uni</country>
<placeName>
<region type="country">Angleterre</region>
</placeName>
<wicri:cityArea>European Medicines Agency (EMEA), Scientific Advice and Orphan Drugs Sector, 7 Westferry Circus, Canary Wharf, London</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Steele, J C" sort="Steele, J C" uniqKey="Steele J" first="J. C." last="Steele">J. C. Steele</name>
<affiliation>
<wicri:noCountry code="subField">Guam</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Tolnay, M" sort="Tolnay, M" uniqKey="Tolnay M" first="M." last="Tolnay">M. Tolnay</name>
<affiliation wicri:level="1">
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Institut für Pathologie, Schönbeinstrasse, Basel</wicri:regionArea>
<wicri:noRegion>Basel</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Tumani, H" sort="Tumani, H" uniqKey="Tumani H" first="H." last="Tumani">H. Tumani</name>
<affiliation wicri:level="4">
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Neurology, University of Ulm, Ulm</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Tübingen</region>
<settlement type="city">Ulm</settlement>
<settlement type="city">Ulm</settlement>
</placeName>
<orgName type="university">Université d'Ulm</orgName>
</affiliation>
</author>
<author>
<name sortKey="Van Swieten, J C" sort="Van Swieten, J C" uniqKey="Van Swieten J" first="J. C." last="Van Swieten">J. C. Van Swieten</name>
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<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>University Hospital Rotterdam, Department of Neurology, Erasmus MC, Dr Molewaterplein, GD Rotterdam</wicri:regionArea>
<wicri:noRegion>GD Rotterdam</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Vanier, M T" sort="Vanier, M T" uniqKey="Vanier M" first="M. T." last="Vanier">M. T. Vanier</name>
<affiliation wicri:level="3">
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Unit 820, Laënnec Medical School, Lyon</wicri:regionArea>
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<name sortKey="Vonsattel, J" sort="Vonsattel, J" uniqKey="Vonsattel J" first="J." last="Vonsattel">J. Vonsattel</name>
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<wicri:regionArea>New York Brain Bank, Columbia University, Pathology, Babies Hospital, New York, NY</wicri:regionArea>
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<settlement type="city">New York</settlement>
</placeName>
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<name sortKey="Wagner, S" sort="Wagner, S" uniqKey="Wagner S" first="S." last="Wagner">S. Wagner</name>
<affiliation wicri:level="3">
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Deutsche PSP‐Gesellschaft e.V. (PSP Germany), c/o S. Wagner, Könneritzstrasse, Leipzig</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Saxe (Land)</region>
<region type="district" nuts="2">District de Leipzig</region>
<settlement type="city">Leipzig</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Wszolek, Z K" sort="Wszolek, Z K" uniqKey="Wszolek Z" first="Z. K." last="Wszolek">Z. K. Wszolek</name>
<affiliation wicri:level="2">
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Mayo Clinic, Department of Neurology, Jacksonville, FL</wicri:regionArea>
<placeName>
<region type="state">Floride</region>
</placeName>
</affiliation>
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<monogr></monogr>
<series>
<title level="j">European Journal of Neurology</title>
<idno type="ISSN">1351-5101</idno>
<idno type="eISSN">1468-1331</idno>
<imprint>
<publisher>Blackwell Publishing Ltd</publisher>
<pubPlace>Oxford, UK</pubPlace>
<date type="published" when="2009-03">2009-03</date>
<biblScope unit="volume">16</biblScope>
<biblScope unit="issue">3</biblScope>
<biblScope unit="page" from="297">297</biblScope>
<biblScope unit="page" to="309">309</biblScope>
</imprint>
<idno type="ISSN">1351-5101</idno>
</series>
<idno type="istex">46DA66675464C537825E2DA84B0B1D58DE536F61</idno>
<idno type="DOI">10.1111/j.1468-1331.2008.02513.x</idno>
<idno type="ArticleID">ENE2513</idno>
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<idno type="ISSN">1351-5101</idno>
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<term>Parkinson disease</term>
<term>corticobasal degeneration</term>
<term>frontotemporal dementia with parkinsonism linked to chromosome 17</term>
<term>microtubule‐associated protein tau</term>
<term>multiple system atrophy</term>
<term>parkinsonism</term>
<term>progressive supranuclear palsy</term>
<term>tauopathies</term>
</keywords>
</textClass>
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<language ident="en">en</language>
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<front>
<div type="abstract" xml:lang="en">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.</div>
</front>
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<title xml:lang="en">Tauopathies with parkinsonism: clinical spectrum, neuropathologic basis, biological markers, and treatment options</title>
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<name sortKey="Ludolph, A C" sort="Ludolph, A C" uniqKey="Ludolph A" first="A. C." last="Ludolph">A. C. Ludolph</name>
<affiliation wicri:level="4">
<nlm:aff id="A1">Department of Neurology, University of Ulm, Ulm, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Neurology, University of Ulm, Ulm</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Tübingen</region>
<settlement type="city">Ulm</settlement>
<settlement type="city">Ulm</settlement>
</placeName>
<orgName type="university">Université d'Ulm</orgName>
</affiliation>
</author>
<author>
<name sortKey="Kassubek, J" sort="Kassubek, J" uniqKey="Kassubek J" first="J." last="Kassubek">J. Kassubek</name>
<affiliation wicri:level="4">
<nlm:aff id="A1">Department of Neurology, University of Ulm, Ulm, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Neurology, University of Ulm, Ulm</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Tübingen</region>
<settlement type="city">Ulm</settlement>
<settlement type="city">Ulm</settlement>
</placeName>
<orgName type="university">Université d'Ulm</orgName>
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<author>
<name sortKey="Landwehrmeyer, B G" sort="Landwehrmeyer, B G" uniqKey="Landwehrmeyer B" first="B. G." last="Landwehrmeyer">B. G. Landwehrmeyer</name>
<affiliation wicri:level="4">
<nlm:aff id="A1">Department of Neurology, University of Ulm, Ulm, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Neurology, University of Ulm, Ulm</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Tübingen</region>
<settlement type="city">Ulm</settlement>
<settlement type="city">Ulm</settlement>
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<orgName type="university">Université d'Ulm</orgName>
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<author>
<name sortKey="Mandelkow, E" sort="Mandelkow, E" uniqKey="Mandelkow E" first="E." last="Mandelkow">E. Mandelkow</name>
<affiliation wicri:level="3">
<nlm:aff id="A2">Max Planck Unit for Structural Molecular Biology, c/o DESY, Notkestr, Hamburg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Max Planck Unit for Structural Molecular Biology, c/o DESY, Notkestr, Hamburg</wicri:regionArea>
<placeName>
<settlement type="city">Hambourg</settlement>
<region type="land" nuts="2">Hambourg</region>
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<author>
<name sortKey="Mandelkow, E M" sort="Mandelkow, E M" uniqKey="Mandelkow E" first="E.-M." last="Mandelkow">E.-M. Mandelkow</name>
<affiliation wicri:level="3">
<nlm:aff id="A2">Max Planck Unit for Structural Molecular Biology, c/o DESY, Notkestr, Hamburg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Max Planck Unit for Structural Molecular Biology, c/o DESY, Notkestr, Hamburg</wicri:regionArea>
<placeName>
<settlement type="city">Hambourg</settlement>
<region type="land" nuts="2">Hambourg</region>
</placeName>
</affiliation>
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<author>
<name sortKey="Burn, D J" sort="Burn, D J" uniqKey="Burn D" first="D. J." last="Burn">D. J. Burn</name>
<affiliation wicri:level="1">
<nlm:aff id="A3">Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne</wicri:regionArea>
<wicri:noRegion>Newcastle upon Tyne</wicri:noRegion>
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</author>
<author>
<name sortKey="Caparros Lefebvre, D" sort="Caparros Lefebvre, D" uniqKey="Caparros Lefebvre D" first="D." last="Caparros-Lefebvre">D. Caparros-Lefebvre</name>
<affiliation wicri:level="3">
<nlm:aff id="A4">Centre Hospitalier de Valenciennes, Résidence du Val d'Escaut, Avenue Desandrouin, Valenciennes, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Centre Hospitalier de Valenciennes, Résidence du Val d'Escaut, Avenue Desandrouin, Valenciennes</wicri:regionArea>
<placeName>
<region type="region">Hauts-de-France</region>
<region type="old region">Nord-Pas-de-Calais</region>
<settlement type="city">Valenciennes</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Frey, K A" sort="Frey, K A" uniqKey="Frey K" first="K. A." last="Frey">K. A. Frey</name>
<affiliation wicri:level="1">
<nlm:aff id="A5">University of Michigan Medical Center, 1500 E Medical Center Dr, Ann Arbor, MI, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>University of Michigan Medical Center, 1500 E Medical Center Dr, Ann Arbor, MI</wicri:regionArea>
<wicri:noRegion>MI</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="De Yebenes, J G" sort="De Yebenes, J G" uniqKey="De Yebenes J" first="J. G." last="De Yebenes">J. G. De Yebenes</name>
<affiliation wicri:level="3">
<nlm:aff id="A6">Hospital Ramon y Cajal, Neurology, Carretera Colmenar, Madrid, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Hospital Ramon y Cajal, Neurology, Carretera Colmenar, Madrid</wicri:regionArea>
<placeName>
<settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Gasser, T" sort="Gasser, T" uniqKey="Gasser T" first="T." last="Gasser">T. Gasser</name>
<affiliation wicri:level="3">
<nlm:aff id="A7">Universitätsklinikum Tübingen, Zentrum für Neurologie, Hoppe-Seyler-Strasse, Tübingen, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Universitätsklinikum Tübingen, Zentrum für Neurologie, Hoppe-Seyler-Strasse, Tübingen</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Tübingen</region>
<settlement type="city">Tübingen</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Heutink, P" sort="Heutink, P" uniqKey="Heutink P" first="P." last="Heutink">P. Heutink</name>
<affiliation wicri:level="3">
<nlm:aff id="A8">VU University Medical Center, Department of Clinical Genetics and Anthropogenet, van der Boechorststraat, Amsterdam, the Netherlands</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>VU University Medical Center, Department of Clinical Genetics and Anthropogenet, van der Boechorststraat, Amsterdam</wicri:regionArea>
<placeName>
<settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Hoglinger, G" sort="Hoglinger, G" uniqKey="Hoglinger G" first="G." last="Höglinger">G. Höglinger</name>
<affiliation wicri:level="3">
<nlm:aff id="A9">Philipps-Universität, Neurologie, Rudolf-Bultmann-Strasse, Marburg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Philipps-Universität, Neurologie, Rudolf-Bultmann-Strasse, Marburg</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Hesse (Land)</region>
<region type="district" nuts="2">District de Giessen</region>
<settlement type="city">Marbourg</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Jamrozik, Z" sort="Jamrozik, Z" uniqKey="Jamrozik Z" first="Z." last="Jamrozik">Z. Jamrozik</name>
<affiliation wicri:level="1">
<nlm:aff id="A10">Medical University of Warsaw, Neurology, Banacha, Warsaw, Poland</nlm:aff>
<country xml:lang="fr">Pologne</country>
<wicri:regionArea>Medical University of Warsaw, Neurology, Banacha, Warsaw</wicri:regionArea>
<wicri:noRegion>Warsaw</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Jellinger, K A" sort="Jellinger, K A" uniqKey="Jellinger K" first="K. A." last="Jellinger">K. A. Jellinger</name>
<affiliation wicri:level="3">
<nlm:aff id="A11">Institute of Clinical Neurobiology, Kenyongasse, Vienna, Austria</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Institute of Clinical Neurobiology, Kenyongasse, Vienna</wicri:regionArea>
<placeName>
<settlement type="city">Vienne (Autriche)</settlement>
<region nuts="2" type="province">Vienne (Autriche)</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Kazantsev, A" sort="Kazantsev, A" uniqKey="Kazantsev A" first="A." last="Kazantsev">A. Kazantsev</name>
<affiliation wicri:level="1">
<nlm:aff id="A12">Massachusetts General Hospital, MIND/Harvard Medical School, Charlestown, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Massachusetts General Hospital, MIND/Harvard Medical School, Charlestown, MA</wicri:regionArea>
<wicri:noRegion>MA</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Kretzschmar, H" sort="Kretzschmar, H" uniqKey="Kretzschmar H" first="H." last="Kretzschmar">H. Kretzschmar</name>
<affiliation wicri:level="3">
<nlm:aff id="A13">Institut für Neuropathologie, BrainNet (German Brain Bank), Feodor-Lynen-Strasse, Munich, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institut für Neuropathologie, BrainNet (German Brain Bank), Feodor-Lynen-Strasse, Munich</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Lang, A E" sort="Lang, A E" uniqKey="Lang A" first="A. E." last="Lang">A. E. Lang</name>
<affiliation wicri:level="1">
<nlm:aff id="A14">Toronto Western Hospital, Movement Disorders Center, Toronto, ON, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Toronto Western Hospital, Movement Disorders Center, Toronto, ON</wicri:regionArea>
<wicri:noRegion>ON</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Litvan, I" sort="Litvan, I" uniqKey="Litvan I" first="I." last="Litvan">I. Litvan</name>
<affiliation wicri:level="1">
<nlm:aff id="A15">University of Louisville, School of Medicine/Department of Neurology, Louisville, KY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>University of Louisville, School of Medicine/Department of Neurology, Louisville, KY</wicri:regionArea>
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<region type="country">Angleterre</region>
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<affiliation wicri:level="2">
<nlm:aff id="A21">European Medicines Agency (EMEA), Scientific Advice and Orphan Drugs Sector, 7 Westferry Circus, Canary Wharf, London, England</nlm:aff>
<country>Royaume-Uni</country>
<placeName>
<region type="country">Angleterre</region>
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<wicri:cityArea>European Medicines Agency (EMEA), Scientific Advice and Orphan Drugs Sector, 7 Westferry Circus, Canary Wharf, London</wicri:cityArea>
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<nlm:aff id="A23">Institut für Pathologie, Schönbeinstrasse, Basel, Switzerland</nlm:aff>
<country xml:lang="fr">Suisse</country>
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<nlm:aff id="A24">University Hospital Rotterdam, Department of Neurology, Erasmus MC, Dr Molewaterplein, GD Rotterdam, the Netherlands</nlm:aff>
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<nlm:aff id="A25">Institut National de la Santé et de la Recherche Médicale, Unit 820, Laeënnec Medical School, Lyon, France</nlm:aff>
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<nlm:aff id="A26">New York Brain Bank, Columbia University, Pathology, Babies Hospital, New York, NY, USA</nlm:aff>
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<nlm:aff id="A27">Deutsche PSP-Gesellschaft e.V. (PSP Germany), c/o S. Wagner, Könneritzstrasse, Leipzig, Germany</nlm:aff>
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<nlm:aff id="A28">Mayo Clinic, Department of Neurology, Jacksonville, FL, USA</nlm:aff>
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<title xml:lang="en" level="a" type="main">Tauopathies with parkinsonism: clinical spectrum, neuropathologic basis, biological markers, and treatment options</title>
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<nlm:aff id="A4">Centre Hospitalier de Valenciennes, Résidence du Val d'Escaut, Avenue Desandrouin, Valenciennes, France</nlm:aff>
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<nlm:aff id="A6">Hospital Ramon y Cajal, Neurology, Carretera Colmenar, Madrid, Spain</nlm:aff>
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<wicri:regionArea>Hospital Ramon y Cajal, Neurology, Carretera Colmenar, Madrid</wicri:regionArea>
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<name sortKey="Gasser, T" sort="Gasser, T" uniqKey="Gasser T" first="T." last="Gasser">T. Gasser</name>
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<nlm:aff id="A7">Universitätsklinikum Tübingen, Zentrum für Neurologie, Hoppe-Seyler-Strasse, Tübingen, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Universitätsklinikum Tübingen, Zentrum für Neurologie, Hoppe-Seyler-Strasse, Tübingen</wicri:regionArea>
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<region type="land" nuts="1">Bade-Wurtemberg</region>
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<nlm:aff id="A8">VU University Medical Center, Department of Clinical Genetics and Anthropogenet, van der Boechorststraat, Amsterdam, the Netherlands</nlm:aff>
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<wicri:regionArea>VU University Medical Center, Department of Clinical Genetics and Anthropogenet, van der Boechorststraat, Amsterdam</wicri:regionArea>
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<settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
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<name sortKey="Hoglinger, G" sort="Hoglinger, G" uniqKey="Hoglinger G" first="G." last="Höglinger">G. Höglinger</name>
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<nlm:aff id="A9">Philipps-Universität, Neurologie, Rudolf-Bultmann-Strasse, Marburg, Germany</nlm:aff>
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<wicri:regionArea>Philipps-Universität, Neurologie, Rudolf-Bultmann-Strasse, Marburg</wicri:regionArea>
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<region type="land" nuts="1">Hesse (Land)</region>
<region type="district" nuts="2">District de Giessen</region>
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<name sortKey="Jamrozik, Z" sort="Jamrozik, Z" uniqKey="Jamrozik Z" first="Z." last="Jamrozik">Z. Jamrozik</name>
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<nlm:aff id="A10">Medical University of Warsaw, Neurology, Banacha, Warsaw, Poland</nlm:aff>
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<name sortKey="Jellinger, K A" sort="Jellinger, K A" uniqKey="Jellinger K" first="K. A." last="Jellinger">K. A. Jellinger</name>
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<name sortKey="Kretzschmar, H" sort="Kretzschmar, H" uniqKey="Kretzschmar H" first="H." last="Kretzschmar">H. Kretzschmar</name>
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<name sortKey="Lucas, J J" sort="Lucas, J J" uniqKey="Lucas J" first="J. J." last="Lucas">J. J. Lucas</name>
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<nlm:aff id="A16">Centro de Biologica Molecular “Severo Ochoa,” Universidad Autonoma de Madrid and CiberNed, Cantoblanco, Madrid, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Centro de Biologica Molecular “Severo Ochoa,” Universidad Autonoma de Madrid and CiberNed, Cantoblanco, Madrid</wicri:regionArea>
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<settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
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</affiliation>
</author>
<author>
<name sortKey="Mcgeer, P L" sort="Mcgeer, P L" uniqKey="Mcgeer P" first="P. L." last="Mcgeer">P. L. Mcgeer</name>
<affiliation wicri:level="1">
<nlm:aff id="A17">University of British Columbia, Kinsmen Laboratory of Neurological Research, Vancouver, BC, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>University of British Columbia, Kinsmen Laboratory of Neurological Research, Vancouver, BC</wicri:regionArea>
<wicri:noRegion>BC</wicri:noRegion>
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<author>
<name sortKey="Melquist, S" sort="Melquist, S" uniqKey="Melquist S" first="S." last="Melquist">S. Melquist</name>
<affiliation wicri:level="1">
<nlm:aff id="A18">Mayo Clinic, Department of Neuroscience, Jacksonville, FL, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Mayo Clinic, Department of Neuroscience, Jacksonville, FL</wicri:regionArea>
<wicri:noRegion>FL</wicri:noRegion>
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</author>
<author>
<name sortKey="Oertel, W" sort="Oertel, W" uniqKey="Oertel W" first="W." last="Oertel">W. Oertel</name>
<affiliation wicri:level="3">
<nlm:aff id="A9">Philipps-Universität, Neurologie, Rudolf-Bultmann-Strasse, Marburg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Philipps-Universität, Neurologie, Rudolf-Bultmann-Strasse, Marburg</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Hesse (Land)</region>
<region type="district" nuts="2">District de Giessen</region>
<settlement type="city">Marbourg</settlement>
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<author>
<name sortKey="Otto, M" sort="Otto, M" uniqKey="Otto M" first="M." last="Otto">M. Otto</name>
<affiliation wicri:level="4">
<nlm:aff id="A1">Department of Neurology, University of Ulm, Ulm, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Neurology, University of Ulm, Ulm</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Tübingen</region>
<settlement type="city">Ulm</settlement>
<settlement type="city">Ulm</settlement>
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<orgName type="university">Université d'Ulm</orgName>
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<name sortKey="Paviour, D" sort="Paviour, D" uniqKey="Paviour D" first="D." last="Paviour">D. Paviour</name>
<affiliation wicri:level="2">
<nlm:aff id="A19">National Hospital for Neurology, Dementia Research Centre, London, England</nlm:aff>
<country>Royaume-Uni</country>
<placeName>
<region type="country">Angleterre</region>
</placeName>
<wicri:cityArea>National Hospital for Neurology, Dementia Research Centre, London</wicri:cityArea>
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<author>
<name sortKey="Reum, T" sort="Reum, T" uniqKey="Reum T" first="T." last="Reum">T. Reum</name>
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<nlm:aff id="A20">Bundesinstitut für Arzneimittel & Medizinprodukte, Wissenschaftlicher Service/Klinische Prüfungen, Georg-Kiesinger-Allee, Bonn, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Bundesinstitut für Arzneimittel & Medizinprodukte, Wissenschaftlicher Service/Klinische Prüfungen, Georg-Kiesinger-Allee, Bonn</wicri:regionArea>
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<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
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</affiliation>
</author>
<author>
<name sortKey="Saint Raymond, A" sort="Saint Raymond, A" uniqKey="Saint Raymond A" first="A." last="Saint-Raymond">A. Saint-Raymond</name>
<affiliation wicri:level="2">
<nlm:aff id="A21">European Medicines Agency (EMEA), Scientific Advice and Orphan Drugs Sector, 7 Westferry Circus, Canary Wharf, London, England</nlm:aff>
<country>Royaume-Uni</country>
<placeName>
<region type="country">Angleterre</region>
</placeName>
<wicri:cityArea>European Medicines Agency (EMEA), Scientific Advice and Orphan Drugs Sector, 7 Westferry Circus, Canary Wharf, London</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Steele, J C" sort="Steele, J C" uniqKey="Steele J" first="J. C." last="Steele">J. C. Steele</name>
<affiliation>
<nlm:aff id="A22">Guam Memorial Hospital, Neurology, Carlos Camacho Way, Tamuning, Guam</nlm:aff>
<wicri:noCountry code="subfield">Guam</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Tolnay, M" sort="Tolnay, M" uniqKey="Tolnay M" first="M." last="Tolnay">M. Tolnay</name>
<affiliation wicri:level="1">
<nlm:aff id="A23">Institut für Pathologie, Schönbeinstrasse, Basel, Switzerland</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Institut für Pathologie, Schönbeinstrasse, Basel</wicri:regionArea>
<wicri:noRegion>Basel</wicri:noRegion>
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<name sortKey="Tumani, H" sort="Tumani, H" uniqKey="Tumani H" first="H." last="Tumani">H. Tumani</name>
<affiliation wicri:level="4">
<nlm:aff id="A1">Department of Neurology, University of Ulm, Ulm, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Neurology, University of Ulm, Ulm</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Tübingen</region>
<settlement type="city">Ulm</settlement>
<settlement type="city">Ulm</settlement>
</placeName>
<orgName type="university">Université d'Ulm</orgName>
</affiliation>
</author>
<author>
<name sortKey="Van Swieten, J C" sort="Van Swieten, J C" uniqKey="Van Swieten J" first="J. C." last="Van Swieten">J. C. Van Swieten</name>
<affiliation wicri:level="1">
<nlm:aff id="A24">University Hospital Rotterdam, Department of Neurology, Erasmus MC, Dr Molewaterplein, GD Rotterdam, the Netherlands</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>University Hospital Rotterdam, Department of Neurology, Erasmus MC, Dr Molewaterplein, GD Rotterdam</wicri:regionArea>
<wicri:noRegion>GD Rotterdam</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Vanier, M T" sort="Vanier, M T" uniqKey="Vanier M" first="M. T." last="Vanier">M. T. Vanier</name>
<affiliation wicri:level="3">
<nlm:aff id="A25">Institut National de la Santé et de la Recherche Médicale, Unit 820, Laeënnec Medical School, Lyon, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Unit 820, Laeënnec Medical School, Lyon</wicri:regionArea>
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<region type="region">Auvergne-Rhône-Alpes</region>
<region type="old region">Rhône-Alpes</region>
<settlement type="city">Lyon</settlement>
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</affiliation>
</author>
<author>
<name sortKey="Vonsattel, J P" sort="Vonsattel, J P" uniqKey="Vonsattel J" first="J.-P." last="Vonsattel">J.-P. Vonsattel</name>
<affiliation wicri:level="4">
<nlm:aff id="A26">New York Brain Bank, Columbia University, Pathology, Babies Hospital, New York, NY, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>New York Brain Bank, Columbia University, Pathology, Babies Hospital, New York, NY</wicri:regionArea>
<orgName type="university">Université Columbia</orgName>
<placeName>
<settlement type="city">New York</settlement>
<region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Wagner, S" sort="Wagner, S" uniqKey="Wagner S" first="S." last="Wagner">S. Wagner</name>
<affiliation wicri:level="3">
<nlm:aff id="A27">Deutsche PSP-Gesellschaft e.V. (PSP Germany), c/o S. Wagner, Könneritzstrasse, Leipzig, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Deutsche PSP-Gesellschaft e.V. (PSP Germany), c/o S. Wagner, Könneritzstrasse, Leipzig</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Saxe (Land)</region>
<region type="district" nuts="2">District de Leipzig</region>
<settlement type="city">Leipzig</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Wszolek, Z K" sort="Wszolek, Z K" uniqKey="Wszolek Z" first="Z. K." last="Wszolek">Z. K. Wszolek</name>
<affiliation wicri:level="1">
<nlm:aff id="A28">Mayo Clinic, Department of Neurology, Jacksonville, FL, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Mayo Clinic, Department of Neurology, Jacksonville, FL</wicri:regionArea>
<wicri:noRegion>FL</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series>
<title level="j">European journal of neurology : the official journal of the European Federation of Neurological Societies</title>
<idno type="ISSN">1351-5101</idno>
<idno type="eISSN">1468-1331</idno>
<imprint>
<date when="2009">2009</date>
</imprint>
</series>
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<front>
<div type="abstract" xml:lang="en">
<p id="P2">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.</p>
</div>
</front>
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