title: Inflammatory profile discriminates clinical subtypes in LRRK2-associated Parkinson's disease.
abstract: 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.
  
  
  
  An extensive battery of peripheral inflammatory markers was measured in human serum in a multicentre cohort of 142 PDLRRK2patients 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.
  
  
  
  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-β (MIP-1-β) 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.
  
  
  
  Inflammation seems to be associated with the presence of a specific clinical subtype in PDLRRK2that 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-β as well as BDNF are interesting candidates to be included in biomarker panels that aim to differentiate subtypes in PDLRRK2and predict progression.
authors.affiliation: Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Brockmann
authors.affiliation: Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Schulte
authors.affiliation: Natural and Medical Sciences Institute at the University of Tübingen (NMI), Reutlingen, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Schneiderhan-Marra
authors.affiliation: Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Apel
authors.affiliation: 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.
authors.forename: C
authors.initials: C
authors.lastname: Pont-Sunyer
authors.affiliation: 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.
authors.forename: D
authors.initials: D
authors.lastname: Vilas
authors.affiliation: Hospital Universitario Donostia, Biodonostia Institut, San Sebastián, Guipuzcoa, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Ruiz-Martinez
authors.affiliation: Mediagnost GmbH, Reutlingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Langkamp
authors.affiliation: Département de Génétique et Cytogénétique, Hôpital de la Pitié Salpêtrière, Sorbonne Universités, INSERM, Paris, France.
authors.forename: J-C
authors.initials: JC
authors.lastname: Corvol
authors.affiliation: Département de Génétique et Cytogénétique, Hôpital de la Pitié Salpêtrière, Sorbonne Universités, INSERM, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Cormier
authors.affiliation: Natural and Medical Sciences Institute at the University of Tübingen (NMI), Reutlingen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Knorpp
authors.affiliation: Natural and Medical Sciences Institute at the University of Tübingen (NMI), Reutlingen, Germany.
authors.forename: T O
authors.initials: TO
authors.lastname: Joos
authors.affiliation: Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Bernard
authors.affiliation: Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Gasser
authors.affiliation: 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.
authors.forename: C
authors.initials: C
authors.lastname: Marras
authors.affiliation: Parkinson Institute and Clinical Center, Sunnyvale, CA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Schüle
authors.affiliation: Department of Neurology, St Olavs Hospital, Trondheim, Norway.
authors.forename: J O
authors.initials: JO
authors.lastname: Aasly
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University, Bloomington, IN, USA.
authors.forename: T
authors.initials: T
authors.lastname: Foroud
authors.affiliation: Hospital Universitario Donostia, Biodonostia Institut, San Sebastián, Guipuzcoa, Spain.
authors.forename: J F
authors.initials: JF
authors.lastname: Marti-Masso
authors.affiliation: Département de Génétique et Cytogénétique, Hôpital de la Pitié Salpêtrière, Sorbonne Universités, INSERM, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Brice
authors.affiliation: 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.
authors.forename: E
authors.initials: E
authors.lastname: Tolosa
authors.affiliation: Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Berg
authors.affiliation: Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Maetzler
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood; D054407:Chemokine CCL4 / Q000097:blood; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology*
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; C111835:CCL2 protein, human; C066507:CCL4 protein, human; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D016207:Cytokines; C579455:BDNF protein, human; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
keywords: 
  LRRK2
  ; Parkinson; inflammation; phenotype