TY - JOUR
T1 - Changes in CD163+, CD11b+, and CCR2+ peripheral monocytes relate to Parkinson's disease and cognition
AU - Konstantin Nissen, Sara
AU - Farmen, Kristine
AU - Carstensen, Mikkel
AU - Schulte, Claudia
AU - Goldeck, David
AU - Brockmann, Kathrin
AU - Romero‐Ramos, Marina
N1 - Funding Information:
We acknowledge the invaluable technical help provided by Gitte Ulbjerg Toft (Department of Biomedicine, Aarhus University). Samples were obtained from the Neuro-Biobank of the University of Tuebingen, Germany (https://www.hih-tuebingen.de/en/about-us/core-facilities/biobank/), which is supported by the local University, the Hertie Institute and the DZNE. Flow cytometry was performed at the FACS Core Facility, Aarhus University, Denmark. Statistical support was provided by the core facility BIostatistical Advisory Service (BIAS) at the Faculty of Health, Aarhus University.
Funding Information:
M. Romero-Ramos serves on the editorial board of Brain Research and npj Parkinson’ disease, and receives research support from Novo Nordisk Foundation, Aarhus University Research Foundation, the Danish Medical Research Council, the Danish Parkinson Foundation, Desiree and Niels Ydes Foundation, and the Michael J Fox Foundation (Grant ID: 15010).
Funding Information:
We acknowledge the invaluable technical help provided by Gitte Ulbjerg Toft (Department of Biomedicine, Aarhus University). Samples were obtained from the Neuro-Biobank of the University of Tuebingen, Germany (https://www.hih-tuebingen.de/en/about-us/core-facilities/biobank/), which is supported by the local University, the Hertie Institute and the DZNE. Flow cytometry was performed at the FACS Core Facility, Aarhus University, Denmark. Statistical support was provided by the core facility BIostatistical Advisory Service (BIAS) at the Faculty of Health, Aarhus University.
Funding Information:
K. Brockmann has received a research grant from the University of Tuebingen (Clinician Scientist), the dPV, the MJFF, and the German Centre for Neurodegenerative Diseases (DZNE, MIGAP); travel grants from the Movement Disorders Society, and speaker honoraria from Abbvie, Lundbeck, UCB, and Zambon.
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/3
Y1 - 2022/3
N2 - Alpha-synuclein pathology is associated with immune activation and neurodegeneration in Parkinson's disease. The immune activation involves not only microglia but also peripheral immune cells, such as mononuclear phagocytes found in blood and infiltrated in the brain. Understanding peripheral immune involvement is essential for developing immunomodulatory treatment. Therefore, we aimed to study circulating mononuclear phagocytes in early- and late-stage Parkinson's disease, defined by disease duration of less or more than five years, respectively, and analyze their association with clinical phenotypes. We performed a cross-sectional multi-color flow cytometry study on 78 sex-balanced individuals with sporadic Parkinson's disease, 28 controls, and longitudinal samples from seven patients and one control. Cell frequencies and surface marker expressions on natural killer cells, monocyte subtypes, and dendritic cells were compared between groups and correlated with standardized clinical scores. We found elevated frequencies and surface levels of migration- (CCR2, CD11b) and phagocytic- (CD163) markers, particularly on classical and intermediate monocytes in early Parkinson's disease. HLA-DR expression was increased in advanced stages of the disease, whereas TLR4 expression was decreased in women with Parkinson's Disease. The disease-associated immune changes of CCR2 and CD11b correlated with worse cognition. Increased TLR2 expression was related to worse motor symptoms. In conclusion, our data highlights the TLR2 relevance in the symptomatic motor presentation of the disease and a role for peripheral CD163+ and migration-competent monocytes in Parkinson's disease cognitive defects. Our study suggests that the peripheral immune system is dynamically altered in Parkinson's disease stages and directly related to both symptoms and the sex bias of the disease.
AB - Alpha-synuclein pathology is associated with immune activation and neurodegeneration in Parkinson's disease. The immune activation involves not only microglia but also peripheral immune cells, such as mononuclear phagocytes found in blood and infiltrated in the brain. Understanding peripheral immune involvement is essential for developing immunomodulatory treatment. Therefore, we aimed to study circulating mononuclear phagocytes in early- and late-stage Parkinson's disease, defined by disease duration of less or more than five years, respectively, and analyze their association with clinical phenotypes. We performed a cross-sectional multi-color flow cytometry study on 78 sex-balanced individuals with sporadic Parkinson's disease, 28 controls, and longitudinal samples from seven patients and one control. Cell frequencies and surface marker expressions on natural killer cells, monocyte subtypes, and dendritic cells were compared between groups and correlated with standardized clinical scores. We found elevated frequencies and surface levels of migration- (CCR2, CD11b) and phagocytic- (CD163) markers, particularly on classical and intermediate monocytes in early Parkinson's disease. HLA-DR expression was increased in advanced stages of the disease, whereas TLR4 expression was decreased in women with Parkinson's Disease. The disease-associated immune changes of CCR2 and CD11b correlated with worse cognition. Increased TLR2 expression was related to worse motor symptoms. In conclusion, our data highlights the TLR2 relevance in the symptomatic motor presentation of the disease and a role for peripheral CD163+ and migration-competent monocytes in Parkinson's disease cognitive defects. Our study suggests that the peripheral immune system is dynamically altered in Parkinson's disease stages and directly related to both symptoms and the sex bias of the disease.
KW - Alpha-synuclein
KW - Dendritic cells
KW - Monocytes
KW - Natural killer cells
KW - Neuroinflammation
KW - Parkinson's disease
KW - TLR
KW - Cross-Sectional Studies
KW - Humans
KW - Parkinson Disease/metabolism
KW - Male
KW - Receptors, Cell Surface
KW - Cognition
KW - Biomarkers/metabolism
KW - Receptors, CCR2/metabolism
KW - Antigens, Differentiation, Myelomonocytic
KW - Toll-Like Receptor 2/metabolism
KW - Female
KW - Antigens, CD
KW - Monocytes/metabolism
UR - http://www.scopus.com/inward/record.url?scp=85122830634&partnerID=8YFLogxK
U2 - 10.1016/j.bbi.2022.01.005
DO - 10.1016/j.bbi.2022.01.005
M3 - Journal article
C2 - 35026420
AN - SCOPUS:85122830634
SN - 0889-1591
VL - 101
SP - 182
EP - 193
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -