PMID- 28102045
OWN - NLM
STAT- MEDLINE
DCOM- 20180103
LR  - 20181202
IS  - 1468-1331 (Electronic)
IS  - 1351-5101 (Linking)
VI  - 24
IP  - 2
DP  - 2017 Feb
TI  - Inflammatory profile discriminates clinical subtypes in LRRK2-associated 
      Parkinson's disease.
PG  - 427-e6
LID - 10.1111/ene.13223 [doi]
AB  - BACKGROUND AND PURPOSE: The presentation of Parkinson's disease patients with 
      mutations in the LRRK2 gene (PD(LRRK)(2) ) 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 PD(LRRK)(2) 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-beta (MIP-1-beta) 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 PD(LRRK)(2) 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-beta as 
      well as BDNF are interesting candidates to be included in biomarker panels that 
      aim to differentiate subtypes in PD(LRRK)(2) and predict progression.
CI  - (c) 2017 EAN.
FAU - Brockmann, K
AU  - Brockmann K
AD  - Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain 
      Research, University of Tubingen, Tubingen, Germany.
AD  - German Center for Neurodegenerative Diseases (DZNE), Tubingen, Germany.
FAU - Schulte, C
AU  - Schulte C
AD  - Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain 
      Research, University of Tubingen, Tubingen, Germany.
AD  - German Center for Neurodegenerative Diseases (DZNE), Tubingen, Germany.
FAU - Schneiderhan-Marra, N
AU  - Schneiderhan-Marra N
AD  - Natural and Medical Sciences Institute at the University of Tubingen (NMI), 
      Reutlingen, Germany.
FAU - Apel, A
AU  - Apel A
AD  - Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain 
      Research, University of Tubingen, Tubingen, Germany.
FAU - Pont-Sunyer, C
AU  - Pont-Sunyer C
AD  - 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 Investigacion Biomedica en 
      Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
FAU - Vilas, D
AU  - Vilas D
AD  - 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 Investigacion Biomedica en 
      Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
FAU - Ruiz-Martinez, J
AU  - Ruiz-Martinez J
AD  - Hospital Universitario Donostia, Biodonostia Institut, San Sebastian, Guipuzcoa, 
      Spain.
FAU - Langkamp, M
AU  - Langkamp M
AD  - Mediagnost GmbH, Reutlingen, Germany.
FAU - Corvol, J-C
AU  - Corvol JC
AD  - Departement de Genetique et Cytogenetique, Hopital de la Pitie Salpetriere, 
      Sorbonne Universites, INSERM, Paris, France.
FAU - Cormier, F
AU  - Cormier F
AD  - Departement de Genetique et Cytogenetique, Hopital de la Pitie Salpetriere, 
      Sorbonne Universites, INSERM, Paris, France.
FAU - Knorpp, T
AU  - Knorpp T
AD  - Natural and Medical Sciences Institute at the University of Tubingen (NMI), 
      Reutlingen, Germany.
FAU - Joos, T O
AU  - Joos TO
AD  - Natural and Medical Sciences Institute at the University of Tubingen (NMI), 
      Reutlingen, Germany.
FAU - Bernard, A
AU  - Bernard A
AD  - Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain 
      Research, University of Tubingen, Tubingen, Germany.
FAU - Gasser, T
AU  - Gasser T
AD  - Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain 
      Research, University of Tubingen, Tubingen, Germany.
AD  - German Center for Neurodegenerative Diseases (DZNE), Tubingen, Germany.
FAU - Marras, C
AU  - Marras C
AD  - 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.
FAU - Schule, B
AU  - Schule B
AD  - Parkinson Institute and Clinical Center, Sunnyvale, CA, USA.
FAU - Aasly, J O
AU  - Aasly JO
AD  - Department of Neurology, St Olavs Hospital, Trondheim, Norway.
FAU - Foroud, T
AU  - Foroud T
AD  - Department of Medical and Molecular Genetics, Indiana University, Bloomington, 
      IN, USA.
FAU - Marti-Masso, J F
AU  - Marti-Masso JF
AD  - Hospital Universitario Donostia, Biodonostia Institut, San Sebastian, Guipuzcoa, 
      Spain.
FAU - Brice, A
AU  - Brice A
AD  - Departement de Genetique et Cytogenetique, Hopital de la Pitie Salpetriere, 
      Sorbonne Universites, INSERM, Paris, France.
FAU - Tolosa, E
AU  - Tolosa E
AD  - 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 Investigacion Biomedica en 
      Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
FAU - Berg, D
AU  - Berg D
AD  - Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain 
      Research, University of Tubingen, Tubingen, Germany.
AD  - German Center for Neurodegenerative Diseases (DZNE), Tubingen, Germany.
FAU - Maetzler, W
AU  - Maetzler W
AD  - Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain 
      Research, University of Tubingen, Tubingen, Germany.
AD  - German Center for Neurodegenerative Diseases (DZNE), Tubingen, Germany.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PL  - England
TA  - Eur J Neurol
JT  - European journal of neurology
JID - 9506311
RN  - 0 (Biomarkers)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (CCL2 protein, human)
RN  - 0 (CCL4 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL4)
RN  - 0 (Cytokines)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - EC 2.7.11.1 (LRRK2 protein, human)
RN  - EC 2.7.11.1 (Leucine-Rich Repeat Serine-Threonine Protein Kinase-2)
SB  - IM
MH  - Adult
MH  - Age of Onset
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers/blood
MH  - Brain-Derived Neurotrophic Factor/blood
MH  - Chemokine CCL2/blood
MH  - Chemokine CCL4/blood
MH  - Cohort Studies
MH  - Cytokines/blood
MH  - Disease Progression
MH  - Female
MH  - Humans
MH  - Inflammation/*etiology/genetics/pathology
MH  - Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/*genetics
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Parkinson Disease/*genetics/*pathology
OTO - NOTNLM
OT  - LRRK2
OT  - Parkinson
OT  - inflammation
OT  - phenotype
EDAT- 2017/01/20 06:00
MHDA- 2018/01/04 06:00
CRDT- 2017/01/20 06:00
PHST- 2016/09/13 00:00 [received]
PHST- 2016/11/07 00:00 [accepted]
PHST- 2017/01/20 06:00 [entrez]
PHST- 2017/01/20 06:00 [pubmed]
PHST- 2018/01/04 06:00 [medline]
AID - 10.1111/ene.13223 [doi]
PST - ppublish
SO  - Eur J Neurol. 2017 Feb;24(2):427-e6. doi: 10.1111/ene.13223.