Inflammatory profile in LRRK2-associated prodromal and clinical PD

Kathrin Brockmann, Anja Apel, Claudia Schulte, Nicole Schneiderhan-Marra, Claustre Pont-Sunyer, Dolores Vilas, Javier Ruiz-Martinez, Markus Langkamp, Jean Christophe Corvol, Florence Cormier, Thomas Knorpp, Thomas O. Joos, Thomas Gasser, Birgitt Schüle, Jan O. Aasly, Tatiana Foroud, Jose Felix Marti-Masso, Alexis Brice, Eduardo Tolosa, Connie MarrasDaniela Berg, Walter Maetzler

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: 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. Methods: We assessed serum profiles of 23 immune-associated markers and the brain-derived neurotrophic factor in 534 individuals from the MJFF LRRK2 consortium. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Article number122
JournalJournal of Neuroinflammation
Volume13
Issue number1
DOIs
StatePublished - May 24 2016

Fingerprint

Parkinson Disease
Prodromal Symptoms
Mutation
Brain-Derived Neurotrophic Factor
Inflammation
Fatty Acid-Binding Proteins
Stem Cell Factor
Microglia
Interleukin-12
Interleukin-10
Immune System
Anti-Inflammatory Agents
Biomarkers
Macrophages
Serum

Keywords

  • Immune
  • Inflammation
  • LRRK2
  • Parkinson

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience
  • Neurology
  • Immunology

Cite this

Brockmann, K., Apel, A., Schulte, C., Schneiderhan-Marra, N., Pont-Sunyer, C., Vilas, D., ... Maetzler, W. (2016). Inflammatory profile in LRRK2-associated prodromal and clinical PD. Journal of Neuroinflammation, 13(1), [122]. https://doi.org/10.1186/s12974-016-0588-5

Inflammatory profile in LRRK2-associated prodromal and clinical PD. / Brockmann, Kathrin; Apel, Anja; Schulte, Claudia; Schneiderhan-Marra, Nicole; Pont-Sunyer, Claustre; Vilas, Dolores; Ruiz-Martinez, Javier; Langkamp, Markus; Corvol, Jean Christophe; Cormier, Florence; Knorpp, Thomas; Joos, Thomas O.; Gasser, Thomas; Schüle, Birgitt; Aasly, Jan O.; Foroud, Tatiana; Marti-Masso, Jose Felix; Brice, Alexis; Tolosa, Eduardo; Marras, Connie; Berg, Daniela; Maetzler, Walter.

In: Journal of Neuroinflammation, Vol. 13, No. 1, 122, 24.05.2016.

Research output: Contribution to journalArticle

Brockmann, K, Apel, A, Schulte, C, Schneiderhan-Marra, N, Pont-Sunyer, C, Vilas, D, Ruiz-Martinez, J, Langkamp, M, Corvol, JC, Cormier, F, Knorpp, T, Joos, TO, Gasser, T, Schüle, B, Aasly, JO, Foroud, T, Marti-Masso, JF, Brice, A, Tolosa, E, Marras, C, Berg, D & Maetzler, W 2016, 'Inflammatory profile in LRRK2-associated prodromal and clinical PD', Journal of Neuroinflammation, vol. 13, no. 1, 122. https://doi.org/10.1186/s12974-016-0588-5
Brockmann K, Apel A, Schulte C, Schneiderhan-Marra N, Pont-Sunyer C, Vilas D et al. Inflammatory profile in LRRK2-associated prodromal and clinical PD. Journal of Neuroinflammation. 2016 May 24;13(1). 122. https://doi.org/10.1186/s12974-016-0588-5
Brockmann, Kathrin ; Apel, Anja ; Schulte, Claudia ; Schneiderhan-Marra, Nicole ; Pont-Sunyer, Claustre ; Vilas, Dolores ; Ruiz-Martinez, Javier ; Langkamp, Markus ; Corvol, Jean Christophe ; Cormier, Florence ; Knorpp, Thomas ; Joos, Thomas O. ; Gasser, Thomas ; Schüle, Birgitt ; Aasly, Jan O. ; Foroud, Tatiana ; Marti-Masso, Jose Felix ; Brice, Alexis ; Tolosa, Eduardo ; Marras, Connie ; Berg, Daniela ; Maetzler, Walter. / Inflammatory profile in LRRK2-associated prodromal and clinical PD. In: Journal of Neuroinflammation. 2016 ; Vol. 13, No. 1.
@article{1cae05aa95744bcaba2422bf7d44bcd7,
title = "Inflammatory profile in LRRK2-associated prodromal and clinical PD",
abstract = "Background: 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. Methods: We assessed serum profiles of 23 immune-associated markers and the brain-derived neurotrophic factor in 534 individuals from the MJFF LRRK2 consortium. Results: 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. Conclusions: 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.",
keywords = "Immune, Inflammation, LRRK2, Parkinson",
author = "Kathrin Brockmann and Anja Apel and Claudia Schulte and Nicole Schneiderhan-Marra and Claustre Pont-Sunyer and Dolores Vilas and Javier Ruiz-Martinez and Markus Langkamp and Corvol, {Jean Christophe} and Florence Cormier and Thomas Knorpp and Joos, {Thomas O.} and Thomas Gasser and Birgitt Sch{\"u}le and Aasly, {Jan O.} and Tatiana Foroud and Marti-Masso, {Jose Felix} and Alexis Brice and Eduardo Tolosa and Connie Marras and Daniela Berg and Walter Maetzler",
year = "2016",
month = "5",
day = "24",
doi = "10.1186/s12974-016-0588-5",
language = "English (US)",
volume = "13",
journal = "Journal of Neuroinflammation",
issn = "1742-2094",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Inflammatory profile in LRRK2-associated prodromal and clinical PD

AU - Brockmann, Kathrin

AU - Apel, Anja

AU - Schulte, Claudia

AU - Schneiderhan-Marra, Nicole

AU - Pont-Sunyer, Claustre

AU - Vilas, Dolores

AU - Ruiz-Martinez, Javier

AU - Langkamp, Markus

AU - Corvol, Jean Christophe

AU - Cormier, Florence

AU - Knorpp, Thomas

AU - Joos, Thomas O.

AU - Gasser, Thomas

AU - Schüle, Birgitt

AU - Aasly, Jan O.

AU - Foroud, Tatiana

AU - Marti-Masso, Jose Felix

AU - Brice, Alexis

AU - Tolosa, Eduardo

AU - Marras, Connie

AU - Berg, Daniela

AU - Maetzler, Walter

PY - 2016/5/24

Y1 - 2016/5/24

N2 - Background: 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. Methods: We assessed serum profiles of 23 immune-associated markers and the brain-derived neurotrophic factor in 534 individuals from the MJFF LRRK2 consortium. Results: 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. Conclusions: 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.

AB - Background: 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. Methods: We assessed serum profiles of 23 immune-associated markers and the brain-derived neurotrophic factor in 534 individuals from the MJFF LRRK2 consortium. Results: 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. Conclusions: 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.

KW - Immune

KW - Inflammation

KW - LRRK2

KW - Parkinson

UR - http://www.scopus.com/inward/record.url?scp=84969921143&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84969921143&partnerID=8YFLogxK

U2 - 10.1186/s12974-016-0588-5

DO - 10.1186/s12974-016-0588-5

M3 - Article

C2 - 27220776

AN - SCOPUS:84969921143

VL - 13

JO - Journal of Neuroinflammation

JF - Journal of Neuroinflammation

SN - 1742-2094

IS - 1

M1 - 122

ER -