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DOI	10.1073/pnas.2020858118
	Monocyte markers correlate with immune and neuronal brain changes in REM sleep behavior disorder
	Farmen K.; Nissen S.K.; Stokholm M.G.; Iranzo A.; Østergaard K.; Serradell M.; Otto M.; Svendsen K.B.; Garrido A.; Vilas D.; Borghammer P.; Santamaria J.; Møller A.; Gaig C.; Brooks D.J.; Tolosa E.; Pavese N.; Romero-Ramos M.
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	Synucleinopathies are neurodegenerative diseases with both central and peripheral immune responses. However, whether the peripheral immune changes occur early in disease and their relation to brain events is yet unclear. Isolated rapid-eye-movement (REM) sleep behavior disorder (iRBD) can precede synucleinopathy-related parkinsonism and provides a prodromal phenotype to study early Parkinson’s disease events. In this prospective case-control study, we describe monocytic markers in a cohort of iRBD patients that were associated with the brain-imaging markers of inflammation and neuronal dysfunction. Using 11C-PK11195 positron emission tomography (PET), we previously showed increased immune activation in the substantia nigra of iRBD patients, while 18F-DOPA PET detected reduced putaminal dopaminergic function. Here we describe that patients’ blood monocytic cells showed increased expression of CD11b, while HLA-DR expression was decreased compared to healthy controls. The iRBD patients had increased classical monocytes and mature natural killer cells. Remarkably, the levels of expression of Toll-like receptor 4 (TLR4) on blood monocytes in iRBD patients were positively correlated with nigral immune activation measured by 11C-PK11195 PET and negatively correlated with putaminal 18F-DOPA uptake; the opposite was seen for the percentage of CD163+ myeloid cells. This suggesting a deleterious role for TLR4 and, conversely, a protective one for the CD163 expression. We show an association between peripheral blood monocytes and brain immune and dopaminergic changes in a synucleinopathy-related disorder, thus suggesting a cross-talk among periphery and brain during the disease. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	CD163; Monocytes; Neuroinflammation; Positron emission tomography; TLR4
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180323
作者单位	Department of Biomedicine, Danish Research Institute of Translational Neuroscience (DANDRITE), Aarhus University, Aarhus, 8000, Denmark; Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, 8200, Denmark; Department of Neurology, Multidisciplinary Sleep Unit, Hospital Clínic de Barcelona, Barcelona, 08036, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, 08007, Spain; Department of Neurology, Aarhus University Hospital, Aarhus, 8200, Denmark; Department of Clinical Neurophysiology, Aarhus University Hospital, Aarhus, 8200, Denmark; Parkinson’s Disease and Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, 08007, Spain; Translational and Clinical Research Institute, Newcastle University, Newcastle, NE1 7RU, United Kingdom
推荐引用方式 GB/T 7714	Farmen K.,Nissen S.K.,Stokholm M.G.,et al. Monocyte markers correlate with immune and neuronal brain changes in REM sleep behavior disorder[J],2021,118(10).
APA	Farmen K..,Nissen S.K..,Stokholm M.G..,Iranzo A..,Østergaard K..,...&Romero-Ramos M..(2021).Monocyte markers correlate with immune and neuronal brain changes in REM sleep behavior disorder.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Farmen K.,et al."Monocyte markers correlate with immune and neuronal brain changes in REM sleep behavior disorder".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).