title: Inflammatory profile in LRRK2-associated prodromal and clinical PD.
abstract: There is evidence for a relevant role of inflammation in the pathogenesis of Parkinson's disease (PD). Mutations in the LRRK2 gene represent the most frequent genetic cause for autosomal dominant PD. LRRK2 is highly expressed in macrophages and microglia suggesting an involvement in inflammatory pathways. The objectives are to test (1) whether idiopathic PD and LRRK2-associated PD share common inflammatory pathways or present distinct profiles and (2) whether non-manifesting LRRK2 mutation carriers present with similar aspects of inflammatory profiles as seen in PD-affected patients.
  
  
  
  We assessed serum profiles of 23 immune-associated markers and the brain-derived neurotrophic factor in 534 individuals from the MJFF LRRK2 consortium.
  
  
  
  A large proportion of inflammatory markers were gender-dependent. Both PD-affected cohorts showed increased levels of the pro-inflammatory marker fatty-acid-binding protein. Additionally, idiopathic PD but not LRRK2-associated PD patients showed increased levels of the pro-inflammatory marker interleukin-12-p40 as well as the anti-inflammatory species interleukin-10, brain-derived neurotrophic factor, and stem cell factor. Non-manifesting LRRK2 mutation carriers including those with prodromal characteristics of PD presented with control-like inflammatory profiles.
  
  
  
  Concomitant inflammation seems to be associated with idiopathic and LRRK2-associated PD. Identifying PD patients in whom inflammatory processes play a major role in their pathophysiology might offer a new therapeutic window at least for a subgroup of patients. Since non-manifesting LRRK2 mutation carriers with symptoms of the prodromal phase of PD did not show inflammatory profiles, activation of the immune system seems not an early event in the disease cascade.
authors.affiliation: Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. Kathrin.Brockmann@uni-tuebingen.de.|German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany. Kathrin.Brockmann@uni-tuebingen.de.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Brockmann
authors.affiliation: Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Apel
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: Claudia
authors.initials: C
authors.lastname: Schulte
authors.affiliation: Natural and Medical Sciences Institute at the University of Tübingen (NMI), Reutlingen, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schneiderhan-Marra
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, Institutd'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Claustre
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, Institutd'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Vilas
authors.affiliation: Hospital Universitario Donostia, Biodonostia Institut, San Sebastián, Guipuzcoa, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Ruiz-Martinez
authors.affiliation: Mediagnost GmbH, Reutlingen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Langkamp
authors.affiliation: Département de Génétique et Cytogénétique, INSERM, Sorbonne Universités, Hôpital de la Pitié Salpêtrière, Paris, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Corvol
authors.affiliation: Département de Génétique et Cytogénétique, INSERM, Sorbonne Universités, Hôpital de la Pitié Salpêtrière, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Cormier
authors.affiliation: Natural and Medical Sciences Institute at the University of Tübingen (NMI), Reutlingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Knorpp
authors.affiliation: Natural and Medical Sciences Institute at the University of Tübingen (NMI), Reutlingen, Germany.
authors.forename: Thomas 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.|German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gasser
authors.affiliation: Parkinson Institute and Clinical Center, 675 Almanor Ave, Sunnyvale, CA, USA.
authors.forename: Birgitt
authors.initials: B
authors.lastname: Schüle
authors.affiliation: Department of Neurology, St. Olavs Hospital, Trondheim, Norway.
authors.forename: Jan O
authors.initials: JO
authors.lastname: Aasly
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University, Bloomington, IN, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
authors.affiliation: Hospital Universitario Donostia, Biodonostia Institut, San Sebastián, Guipuzcoa, Spain.
authors.forename: Jose Felix
authors.initials: JF
authors.lastname: Marti-Masso
authors.affiliation: Département de Génétique et Cytogénétique, INSERM, Sorbonne Universités, Hôpital de la Pitié Salpêtrière, Paris, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, Institutd'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tolosa
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, Canada.
authors.forename: Connie
authors.initials: C
authors.lastname: Marras
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: Daniela
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: Walter
authors.initials: W
authors.lastname: Maetzler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001672:Biocompatible Materials / Q000378:metabolism; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007391:International Cooperation; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000097:blood* / Q000235:genetics*; D012189:Retrospective Studies; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D001672:Biocompatible Materials; D016207:Cytokines; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D018664:Interleukin-12; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
keywords: Immune; Inflammation; LRRK2; Parkinson