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Inflammatory profile discriminates clinical subtypes in LRRK2-associated Parkinson's disease.
Brockmann, K; Schulte, C; Schneiderhan-Marra, N; Apel, A; Pont-Sunyer, C; Vilas, D; Ruiz-Martinez, J; Langkamp, M; Corvol, J-C; Cormier, F; Knorpp, T; Joos, T O; Bernard, A; Gasser, T; Marras, C; Schüle, B; Aasly, J O; Foroud, T; Marti-Masso, J F; Brice, A; Tolosa, E; Berg, D; Maetzler, W.
Afiliación
  • Brockmann K; Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
  • Schulte C; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
  • Schneiderhan-Marra N; Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
  • Apel A; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
  • Pont-Sunyer C; Natural and Medical Sciences Institute at the University of Tübingen (NMI), Reutlingen, Germany.
  • Vilas D; Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
  • Ruiz-Martinez J; Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
  • Langkamp M; Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
  • Corvol JC; Hospital Universitario Donostia, Biodonostia Institut, San Sebastián, Guipuzcoa, Spain.
  • Cormier F; Mediagnost GmbH, Reutlingen, Germany.
  • Knorpp T; Département de Génétique et Cytogénétique, Hôpital de la Pitié Salpêtrière, Sorbonne Universités, INSERM, Paris, France.
  • Joos TO; Département de Génétique et Cytogénétique, Hôpital de la Pitié Salpêtrière, Sorbonne Universités, INSERM, Paris, France.
  • Bernard A; Natural and Medical Sciences Institute at the University of Tübingen (NMI), Reutlingen, Germany.
  • Gasser T; Natural and Medical Sciences Institute at the University of Tübingen (NMI), Reutlingen, Germany.
  • Marras C; Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
  • Schüle B; Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
  • Aasly JO; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
  • Foroud T; Morton and Gloria Shulman Movement Disorders Centre and the Edmond J Safra Program in Parkinson's Disease, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada.
  • Marti-Masso JF; Parkinson Institute and Clinical Center, Sunnyvale, CA, USA.
  • Brice A; Department of Neurology, St Olavs Hospital, Trondheim, Norway.
  • Tolosa E; Department of Medical and Molecular Genetics, Indiana University, Bloomington, IN, USA.
  • Berg D; Hospital Universitario Donostia, Biodonostia Institut, San Sebastián, Guipuzcoa, Spain.
  • Maetzler W; Département de Génétique et Cytogénétique, Hôpital de la Pitié Salpêtrière, Sorbonne Universités, INSERM, Paris, France.
Eur J Neurol ; 24(2): 427-e6, 2017 02.
Article en En | MEDLINE | ID: mdl-28102045
BACKGROUND AND PURPOSE: The presentation of Parkinson's disease patients with mutations in the LRRK2 gene (PDLRRK2 ) is highly variable, suggesting a strong influence of modifying factors. In this context, inflammation is a potential candidate inducing clinical subtypes. METHODS: An extensive battery of peripheral inflammatory markers was measured in human serum in a multicentre cohort of 142 PDLRRK2 patients from the MJFF LRRK2 Consortium, stratified by three different subtypes as recently proposed for idiopathic Parkinson's disease: diffuse/malignant, intermediate and mainly pure motor. RESULTS: Patients classified as diffuse/malignant presented with the highest levels of the pro-inflammatory proteins interleukin 8 (IL-8), monocyte chemotactic protein 1 (MCP-1) and macrophage inflammatory protein 1-ß (MIP-1-ß) paralleled by high levels of the neurotrophic protein brain-derived neurotrophic factor (BDNF). It was also possible to distinguish the clinical subtypes based on their inflammatory profile by using discriminant and area under the receiver operating characteristic curve analysis. CONCLUSIONS: Inflammation seems to be associated with the presence of a specific clinical subtype in PDLRRK2 that is characterized by a broad and more severely affected spectrum of motor and non-motor symptoms. The pro-inflammatory metabolites IL-8, MCP-1 and MIP-1-ß as well as BDNF are interesting candidates to be included in biomarker panels that aim to differentiate subtypes in PDLRRK2 and predict progression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina / Inflamación Tipo de estudio: Clinical_trials / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Eur J Neurol Asunto de la revista: NEUROLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina / Inflamación Tipo de estudio: Clinical_trials / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Eur J Neurol Asunto de la revista: NEUROLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido