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In addition to being a prodromal symptom of PD, RBD has a major negative impact on the prognosis of PD patients. This intrinsic connection indicates that there is a bidirectional relationship between PD and RBD. This paper provides a comprehensive review of the pathological mechanism related to PD and RBD, including the \u03b1-synuclein pathological deposition, abnormal iron metabolism, neuroinflammation, glymphatic system dysfunction and dysbiosis of the gut microbiota. Increasing evidence has shown that RBD patients have the same pathogenic mechanisms that underlie PD, but relatively little research has been done on how RBD contributes to PD progression. Therefore, a more thorough investigation is warranted to characterise how RBD affects the course of PD, in order to prepare for future therapeutic trials.<\/jats:p>","DOI":"10.31083\/j.jin2309166","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T03:16:33Z","timestamp":1727320593000},"source":"Crossref","is-referenced-by-count":14,"title":["Research Progress on the Relationship between Parkinson's Disease and REM Sleep Behavior Disorder"],"prefix":"10.31083","volume":"23","author":[{"given":"Yu","family":"Zhou","sequence":"first","affiliation":[{"name":"The Second Clinical Medical College of Zhejiang Chinese Medical University, 310000 Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurology, Zhejiang Hospital Affiliated to Zhejiang University, 310000 Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, 310000 Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2024,9,14]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Bloem BR, Okun MS, Klein C. Parkinson\u2019s disease. Lancet (London, England). 2021; 397: 2284\u20132303.","DOI":"10.1016\/S0140-6736(21)00218-X"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Liguori C, De Franco V, Cerroni R, Spanetta M, Mercuri NB, Stefani A, et al. Sleep problems affect quality of life in Parkinson\u2019s disease along disease progression. Sleep Medicine. 2021; 81: 307\u2013311.","DOI":"10.1016\/j.sleep.2021.02.036"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Barone P, Antonini A, Colosimo C, Marconi R, Morgante L, Avarello TP, et al. The PRIAMO study: A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson\u2019s disease. Movement Disorders: Official Journal of the Movement Disorder Society. 2009; 24: 1641\u20131649.","DOI":"10.1002\/mds.22643"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Keir LHM, Breen DP. New awakenings: current understanding of sleep dysfunction and its treatment in Parkinson\u2019s disease. Journal of Neurology. 2020; 267: 288\u2013294.","DOI":"10.1007\/s00415-019-09651-z"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Barone DA, Henchcliffe C. Rapid eye movement sleep behavior disorder and the link to alpha-synucleinopathies. Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology. 2018; 129: 1551\u20131564.","DOI":"10.1016\/j.clinph.2018.05.003"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Schenck CH, Mahowald MW. REM sleep behavior disorder: clinical, developmental, and neuroscience perspectives 16 years after its formal identification in SLEEP. Sleep. 2002; 25: 120\u2013138.","DOI":"10.1093\/sleep\/25.2.120"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Roguski A, Rayment D, Whone AL, Jones MW, Rolinski M. A Neurologist\u2019s Guide to REM Sleep Behavior Disorder. Frontiers in Neurology. 2020; 11: 610.","DOI":"10.3389\/fneur.2020.00610"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Hu MT. REM sleep behavior disorder (RBD). Neurobiology of Disease. 2020; 143: 104996.","DOI":"10.1016\/j.nbd.2020.104996"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"St Louis EK, Boeve BF. REM Sleep Behavior Disorder: Diagnosis, Clinical Implications, and Future Directions. Mayo Clinic Proceedings. 2017; 92: 1723\u20131736.","DOI":"10.1016\/j.mayocp.2017.09.007"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Dauvilliers Y, Schenck CH, Postuma RB, Iranzo A, Luppi PH, Plazzi G, et al. REM sleep behaviour disorder. Nature Reviews. Disease Primers. 2018; 4: 19.","DOI":"10.1038\/s41572-018-0016-5"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Rodriguez CL, Jaimchariyatam N, Budur K. Rapid Eye Movement Sleep Behavior Disorder: A Review of the Literature and Update on Current Concepts. Chest. 2017; 152: 650\u2013662.","DOI":"10.1016\/j.chest.2017.03.015"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Mahowald MW, Schenck CH, Bornemann MAC. Pathophysiologic mechanisms in REM sleep behavior disorder. Current Neurology and Neuroscience Reports. 2007; 7: 167\u2013172.","DOI":"10.1007\/s11910-007-0013-7"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Iranzo A, Tolosa E, Gelpi E, Molinuevo JL, Valldeoriola F, Serradell M, et al. Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study. The Lancet. Neurology. 2013; 12: 443\u2013453.","DOI":"10.1016\/S1474-4422(13)70056-5"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"McKenna D, Peever J. Degeneration of rapid eye movement sleep circuitry underlies rapid eye movement sleep behavior disorder. Movement Disorders: Official Journal of the Movement Disorder Society. 2017; 32: 636\u2013644.","DOI":"10.1002\/mds.27003"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Nomura T, Inoue Y, H\u00f6gl B, Uemura Y, Kitayama M, Abe T, et al. Relationship between (123)I-MIBG scintigrams and REM sleep behavior disorder in Parkinson\u2019s disease. Parkinsonism & Related Disorders. 2010; 16: 683\u2013685.","DOI":"10.1016\/j.parkreldis.2010.08.011"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Mao J, Huang X, Yu J, Chen L, Huang Y, Tang B, et al. Association Between REM Sleep Behavior Disorder and Cognitive Dysfunctions in Parkinson\u2019s Disease: A Systematic Review and Meta-Analysis of Observational Studies. Frontiers in Neurology. 2020; 11: 577874.","DOI":"10.3389\/fneur.2020.577874"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Miyamoto M, Miyamoto T. Relationship of substantia nigra hyperechogenicity to risk of Lewy body disease in idiopathic REM sleep behavior disorder patients: a longitudinal study. Sleep Medicine. 2020; 68: 31\u201334.","DOI":"10.1016\/j.sleep.2019.09.008"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Gagnon JF, Postuma RB, Mazza S, Doyon J, Montplaisir J. Rapid-eye-movement sleep behaviour disorder and neurodegenerative diseases. The Lancet. Neurology. 2006; 5: 424\u2013432.","DOI":"10.1016\/S1474-4422(06)70441-0"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Li M, Wang L, Liu JH, Zhan SQ. Relationships between Rapid Eye Movement Sleep Behavior Disorder and Neurodegenerative Diseases: Clinical Assessments, Biomarkers, and Treatment. Chinese Medical Journal. 2018; 131: 966\u2013973.","DOI":"10.4103\/0366-6999.229886"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Postuma RB, Iranzo A, Hu M, H\u00f6gl B, Boeve BF, Manni R, et al. Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. Brain: a Journal of Neurology. 2019; 142: 744\u2013759.","DOI":"10.1093\/brain\/awz030"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Braak H, Del Tredici K, R\u00fcb U, de Vos RAI, Jansen Steur ENH, Braak E. Staging of brain pathology related to sporadic Parkinson\u2019s disease. Neurobiology of Aging. 2003; 24: 197\u2013211.","DOI":"10.1016\/S0197-4580(02)00065-9"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Zhang F, Niu L, Liu X, Liu Y, Li S, Yu H, et al. Rapid Eye Movement Sleep Behavior Disorder and Neurodegenerative Diseases: An Update. Aging and Disease. 2020; 11: 315\u2013326.","DOI":"10.14336\/AD.2019.0324"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Iranzo A, Lome\u00f1a F, Stockner H, Valldeoriola F, Vilaseca I, Salamero M, et al. Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study [corrected]. The Lancet. Neurology. 2010; 9: 1070\u20131077.","DOI":"10.1016\/S1474-4422(10)70216-7"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Sun J, Lai Z, Ma J, Gao L, Chen M, Chen J, et al. Quantitative evaluation of iron content in idiopathic rapid eye movement sleep behavior disorder. Movement Disorders: Official Journal of the Movement Disorder Society. 2020; 35: 478\u2013485.","DOI":"10.1002\/mds.27929"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Tan S, Zhou C, Wen J, Duanmu X, Guo T, Wu H, et al. Presence but not the timing of onset of REM sleep behavior disorder distinguishes evolution patterns in Parkinson\u2019s disease. Neurobiology of Disease. 2023; 180: 106084.","DOI":"10.1016\/j.nbd.2023.106084"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Riboldi GM, Russo MJ, Pan L, Watkins K, Kang UJ. Dysautonomia and REM sleep behavior disorder contributions to progression of Parkinson\u2019s disease phenotypes. NPJ Parkinson\u2019s disease. 2022; 8: 110.","DOI":"10.1038\/s41531-022-00373-0"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Fereshtehnejad SM, Postuma RB. Subtypes of Parkinson\u2019s disease: What Do They Tell Us About Disease Progression? Current Neurology and Neuroscience Reports. 2017; 17: 34.","DOI":"10.1007\/s11910-017-0738-x"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Fereshtehnejad SM, Zeighami Y, Dagher A, Postuma RB. Clinical criteria for subtyping Parkinson\u2019s disease: biomarkers and longitudinal progression. Brain: a Journal of Neurology. 2017; 140: 1959\u20131976.","DOI":"10.1093\/brain\/awx118"},{"key":"ref29","doi-asserted-by":"crossref","unstructured":"Iranzo A, Santamaria J, Tolosa E. The clinical and pathophysiological relevance of REM sleep behavior disorder in neurodegenerative diseases. Sleep Medicine Reviews. 2009; 13: 385\u2013401.","DOI":"10.1016\/j.smrv.2008.11.003"},{"key":"ref30","doi-asserted-by":"crossref","unstructured":"Vendette M, Gagnon J-F, D\u00e9cary A, Massicotte-Marquez J, Postuma R B, Doyon J, et al. REM sleep behavior disorder predicts cognitive impairment in Parkinson disease without dementia. Neurology. 2007; 69: 1843\u20131849.","DOI":"10.1212\/01.wnl.0000278114.14096.74"},{"key":"ref31","doi-asserted-by":"crossref","unstructured":"Fantini ML, Figorilli M, Arnulf I, Zibetti M, Pereira B, Beudin P, et al. Sleep and REM sleep behaviour disorder in Parkinson\u2019s disease with impulse control disorder. Journal of Neurology, Neurosurgery, and Psychiatry. 2018; 89: 305\u2013310.","DOI":"10.1136\/jnnp-2017-316576"},{"key":"ref32","doi-asserted-by":"crossref","unstructured":"Shulman JM, De Jager PL, Feany MB. Parkinson\u2019s disease: genetics and pathogenesis. Annual Review of Pathology. 2011; 6: 193\u2013222.","DOI":"10.1146\/annurev-pathol-011110-130242"},{"key":"ref33","doi-asserted-by":"crossref","unstructured":"Ulusoy A, Phillips RJ, Helwig M, Klinkenberg M, Powley TL, Di Monte DA. Brain-to-stomach transfer of \u03b1-synuclein via vagal preganglionic projections. Acta Neuropathologica. 2017; 133: 381\u2013393.","DOI":"10.1007\/s00401-016-1661-y"},{"key":"ref34","doi-asserted-by":"crossref","unstructured":"George S, Rey NL, Tyson T, Esquibel C, Meyerdirk L, Schulz E, et al. Microglia affect \u03b1-synuclein cell-to-cell transfer in a mouse model of Parkinson\u2019s disease. Molecular Neurodegeneration. 2019; 14: 34.","DOI":"10.1186\/s13024-019-0335-3"},{"key":"ref35","doi-asserted-by":"crossref","unstructured":"Zitser J, Gibbons C, Miglis MG. The role of tissue biopsy as a biomarker in REM sleep behavior disorder. Sleep Medicine Reviews. 2020; 51: 101283.","DOI":"10.1016\/j.smrv.2020.101283"},{"key":"ref36","doi-asserted-by":"crossref","unstructured":"Iranzo A, Mammana A, Mu\u00f1oz-Lopetegi A, Dellavalle S, May\u00e0 G, Rossi M, et al. Misfolded \u03b1-Synuclein Assessment in the Skin and CSF by RT-QuIC in Isolated REM Sleep Behavior Disorder. Neurology. 2023; 100: e1944\u2013e1954.","DOI":"10.1212\/WNL.0000000000207147"},{"key":"ref37","doi-asserted-by":"crossref","unstructured":"Iranzo A, Fairfoul G, Ayudhaya ACN, Serradell M, Gelpi E, Vilaseca I, et al. Detection of \u03b1-synuclein in CSF by RT-QuIC in patients with isolated rapid-eye-movement sleep behaviour disorder: a longitudinal observational study. The Lancet. Neurology. 2021; 20: 203\u2013212.","DOI":"10.1016\/S1474-4422(20)30449-X"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"Iranzo A, Borrego S, Vilaseca I, Mart\u00ed C, Serradell M, S\u00e1nchez-Valle R, et al. \u03b1-Synuclein aggregates in labial salivary glands of idiopathic rapid eye movement sleep behavior disorder. Sleep. 2018; 41:","DOI":"10.1093\/sleep\/zsy101."},{"key":"ref39","doi-asserted-by":"crossref","unstructured":"Dolatshahi M, Pourmirbabaei S, Kamalian A, Ashraf-Ganjouei A, Yaseri M, Aarabi MH. Longitudinal Alterations of Alpha-Synuclein, Amyloid Beta, Total, and Phosphorylated Tau in Cerebrospinal Fluid and Correlations Between Their Changes in Parkinson\u2019s disease. Frontiers in Neurology. 2018; 9: 560.","DOI":"10.3389\/fneur.2018.00560"},{"key":"ref40","doi-asserted-by":"crossref","unstructured":"Hu Y, Yu SY, Zuo LJ, Cao CJ, Wang F, Chen ZJ, et al. Parkinson disease with REM sleep behavior disorder: features, \u03b1-synuclein, and inflammation. Neurology. 2015; 84: 888\u2013894.","DOI":"10.1212\/WNL.0000000000001308"},{"key":"ref41","doi-asserted-by":"crossref","unstructured":"Goldman JG, Andrews H, Amara A, Naito A, Alcalay RN, Shaw LM, et al. Cerebrospinal fluid, plasma, and saliva in the BioFIND study: Relationships among biomarkers and Parkinson\u2019s disease Features. Movement Disorders: Official Journal of the Movement Disorder Society. 2018; 33: 282\u2013288.","DOI":"10.1002\/mds.27232"},{"key":"ref42","doi-asserted-by":"crossref","unstructured":"Nabizadeh F, Pirahesh K, Valizadeh P. REM sleep behavior disorder and cerebrospinal fluid alpha-synuclein, amyloid beta, total tau and phosphorylated tau in Parkinson\u2019s disease: a cross-sectional and longitudinal study. Journal of Neurology. 2022; 269: 4836\u20134845.","DOI":"10.1007\/s00415-022-11120-z"},{"key":"ref43","doi-asserted-by":"crossref","unstructured":"Zucca FA, Segura-Aguilar J, Ferrari E, Mu\u00f1oz P, Paris I, Sulzer D, et al. Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson\u2019s disease. Progress in Neurobiology. 2017; 155: 96\u2013119.","DOI":"10.1016\/j.pneurobio.2015.09.012"},{"key":"ref44","doi-asserted-by":"crossref","unstructured":"Long H, Zhu W, Wei L, Zhao J. Iron homeostasis imbalance and ferroptosis in brain diseases. MedComm. 2023; 4: e298.","DOI":"10.1002\/mco2.298"},{"key":"ref45","doi-asserted-by":"crossref","unstructured":"Khedher L, Bonny JM, Marques A, Durand E, Pereira B, Chupin M, et al. Intrasubject subcortical quantitative referencing to boost MRI sensitivity to Parkinson\u2019s disease. NeuroImage. Clinical. 2022; 36: 103231.","DOI":"10.1016\/j.nicl.2022.103231"},{"key":"ref46","doi-asserted-by":"crossref","unstructured":"Castellani R J, Siedlak S L, Perry G, Smith M A. Sequestration of iron by Lewy bodies in Parkinson\u2019s disease. Acta Neuropathologica. 2000; 100: 111\u2013114.","DOI":"10.1007\/s004010050001"},{"key":"ref47","doi-asserted-by":"crossref","unstructured":"Mahul-Mellier A L, Burtscher J, Maharjan N, Weerens L, Croisier M, Kuttler F, et al. The process of Lewy body formation, rather than simply \u03b1-synuclein fibrillization, is one of the major drivers of neurodegeneration. Proceedings of the National Academy of Sciences of the United States of America. 2020; 117: 4971\u20134982.","DOI":"10.1073\/pnas.1913904117"},{"key":"ref48","doi-asserted-by":"crossref","unstructured":"Guo J J, Yue F, Song D Y, Bousset L, Liang X, Tang J, et al. Intranasal administration of \u03b1-synuclein preformed fibrils triggers microglial iron deposition in the substantia nigra of Macaca fascicularis. Cell Death & Disease. 2021; 12: 81.","DOI":"10.1038\/s41419-020-03369-x"},{"key":"ref49","doi-asserted-by":"crossref","unstructured":"Lakhani DA, Middlebrooks EH. 7-T Neuromelanin and R2* MRI in Parkinson Disease. Radiology. 2022; 305: 296.","DOI":"10.1148\/radiol.220230"},{"key":"ref50","doi-asserted-by":"crossref","unstructured":"Hansen A K, Knudsen K, Lillethorup T P, Landau A M, Parbo P, Fedorova T, et al. In vivo imaging of neuromelanin in Parkinson\u2019s disease using 18F-AV-1451 PET. Brain. 2016, 139: 2039\u20132049.","DOI":"10.1093\/brain\/aww098"},{"key":"ref51","doi-asserted-by":"crossref","unstructured":"Biondetti E, Santin MD, Valabr\u00e8gue R, Mangone G, Gaurav R, Pyatigorskaya N, et al. The spatiotemporal changes in dopamine, neuromelanin and iron characterizing Parkinson\u2019s disease. Brain: a Journal of Neurology. 2021; 144: 3114\u20133125.","DOI":"10.1093\/brain\/awab191"},{"key":"ref52","doi-asserted-by":"crossref","unstructured":"Lee JH, Han YH, Cho JW, Lee JS, Lee SJ, Kim DJ, et al. Evaluation of brain iron content in idiopathic REM sleep behavior disorder using quantitative magnetic resonance imaging. Parkinsonism & Related Disorders. 2014; 20: 776\u2013778.","DOI":"10.1016\/j.parkreldis.2014.03.023"},{"key":"ref53","doi-asserted-by":"publisher","unstructured":"Pyatigorskaya N, Gaurav R, Arnaldi D, Leu-Semenescu S, Yahia-Cherif L, Valabregue R, et al. Magnetic Resonance Imaging Biomarkers to Assess Substantia Nigra Damage in Idiopathic Rapid Eye Movement Sleep Behavior Disorder. Sleep. 2017; 40:","DOI":"10.1093\/sleep\/zsx149."},{"key":"ref54","doi-asserted-by":"crossref","unstructured":"Biondetti E, Gaurav R, Yahia-Cherif L, Mangone G, Pyatigorskaya N, Valabr\u00e8gue R, et al. Spatiotemporal changes in substantia nigra neuromelanin content in Parkinson\u2019s disease. Brain: a Journal of Neurology. 2020; 143: 2757\u20132770.","DOI":"10.1093\/brain\/awaa216"},{"key":"ref55","doi-asserted-by":"crossref","unstructured":"Knudsen K, Fedorova TD, Hansen AK, Sommerauer M, Otto M, Svendsen KB, et al. In-vivo staging of pathology in REM sleep behaviour disorder: a multimodality imaging case-control study. The Lancet. Neurology. 2018; 17: 618\u2013628.","DOI":"10.1016\/S1474-4422(18)30162-5"},{"key":"ref56","doi-asserted-by":"crossref","unstructured":"Ehrminger M, Latimier A, Pyatigorskaya N, Garcia-Lorenzo D, Leu-Semenescu S, Vidailhet M, et al. The coeruleus\/subcoeruleus complex in idiopathic rapid eye movement sleep behaviour disorder. Brain: a Journal of Neurology. 2016; 139: 1180\u20131188.","DOI":"10.1093\/brain\/aww006"},{"key":"ref57","doi-asserted-by":"crossref","unstructured":"Pimer LJ, Leslie RA, Phillips G, Newman AJ, Rusak B, Rolheiser TM, et al. Aberrant corticospinal tract characteristics in prodromal PD: A diffusion tensor imaging study. Clinical Parkinsonism & Related Disorders. 2022; 8: 100182.","DOI":"10.1016\/j.prdoa.2022.100182"},{"key":"ref58","doi-asserted-by":"crossref","unstructured":"Calabresi P, Mechelli A, Natale G, Volpicelli-Daley L, Di Lazzaro G, Ghiglieri V. Alpha-synuclein in Parkinson\u2019s disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction. Cell Death & Disease. 2023; 14: 176.","DOI":"10.1038\/s41419-023-05672-9"},{"key":"ref59","doi-asserted-by":"crossref","unstructured":"Orr CF, Rowe DB, Mizuno Y, Mori H, Halliday GM. A possible role for humoral immunity in the pathogenesis of Parkinson\u2019s disease. Brain: a Journal of Neurology. 2005; 128: 2665\u20132674.","DOI":"10.1093\/brain\/awh625"},{"key":"ref60","doi-asserted-by":"crossref","unstructured":"Hirsch EC, Hunot S. Neuroinflammation in Parkinson\u2019s disease: a target for neuroprotection? The Lancet. Neurology. 2009; 8: 382\u2013397.","DOI":"10.1016\/S1474-4422(09)70062-6"},{"key":"ref61","doi-asserted-by":"crossref","unstructured":"Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms underlying inflammation in neurodegeneration. Cell. 2010; 140: 918\u2013934.","DOI":"10.1016\/j.cell.2010.02.016"},{"key":"ref62","doi-asserted-by":"crossref","unstructured":"Liu SY, Qiao HW, Song TB, Liu XL, Yao YX, Zhao CS, et al. Brain microglia activation and peripheral adaptive immunity in Parkinson\u2019s disease: a multimodal PET study. Journal of Neuroinflammation. 2022; 19: 209.","DOI":"10.1186\/s12974-022-02574-z"},{"key":"ref63","doi-asserted-by":"crossref","unstructured":"Qin XY, Zhang SP, Cao C, Loh YP, Cheng Y. Aberrations in Peripheral Inflammatory Cytokine Levels in Parkinson Disease: A Systematic Review and Meta-analysis. JAMA Neurology. 2016; 73: 1316\u20131324.","DOI":"10.1001\/jamaneurol.2016.2742"},{"key":"ref64","doi-asserted-by":"crossref","unstructured":"Stokholm MG, Iranzo A, \u00d8stergaard K, Serradell M, Otto M, Svendsen KB, et al. Assessment of neuroinflammation in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a case-control study. The Lancet. Neurology. 2017; 16: 789\u2013796.","DOI":"10.1016\/S1474-4422(17)30173-4"},{"key":"ref65","doi-asserted-by":"crossref","unstructured":"Kim R, Jun JS, Kim HJ, Jung KY, Shin YW, Yang TW, et al. Peripheral Blood Inflammatory Cytokines in Idiopathic REM Sleep Behavior Disorder. Movement Disorders: Official Journal of the Movement Disorder Society. 2019; 34: 1739\u20131744.","DOI":"10.1002\/mds.27841"},{"key":"ref66","doi-asserted-by":"crossref","unstructured":"Farmen K, Nissen SK, Stokholm MG, Iranzo A, \u00d8stergaard K, Serradell M, 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. 2021; 118: e2020858118.","DOI":"10.1073\/pnas.2020858118"},{"key":"ref67","doi-asserted-by":"crossref","unstructured":"De Francesco E, Terzaghi M, Storelli E, Magistrelli L, Comi C, Legnaro M, et al. CD4+ T-cell Transcription Factors in Idiopathic REM Sleep Behavior Disorder and Parkinson\u2019s disease. Movement Disorders: Official Journal of the Movement Disorder Society. 2021; 36: 225\u2013229.","DOI":"10.1002\/mds.28137"},{"key":"ref68","doi-asserted-by":"crossref","unstructured":"Abbott NJ, Pizzo ME, Preston JE, Janigro D, Thorne RG. The role of brain barriers in fluid movement in the CNS: is there a \u2019glymphatic\u2019 system? 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Frontiers in Aging Neuroscience. 2021; 13: 773951.","DOI":"10.3389\/fnagi.2021.773951"},{"key":"ref72","doi-asserted-by":"crossref","unstructured":"Fultz NE, Bonmassar G, Setsompop K, Stickgold RA, Rosen BR, Polimeni JR, et al. Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep. Science (New York, N.Y.). 2019; 366: 628\u2013631.","DOI":"10.1126\/science.aax5440"},{"key":"ref73","doi-asserted-by":"crossref","unstructured":"Zou W, Pu T, Feng W, Lu M, Zheng Y, Du R, et al. Blocking meningeal lymphatic drainage aggravates Parkinson\u2019s disease-like pathology in mice overexpressing mutated \u03b1-synuclein. Translational Neurodegeneration. 2019; 8: 7.","DOI":"10.1186\/s40035-019-0147-y"},{"key":"ref74","doi-asserted-by":"crossref","unstructured":"Si XL, Gu LY, Song Z, Zhou C, Fang Y, Jin CY, et al. Different Perivascular Space Burdens in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson\u2019s disease. Frontiers in Aging Neuroscience. 2020; 12: 580853.","DOI":"10.3389\/fnagi.2020.580853"},{"key":"ref75","doi-asserted-by":"crossref","unstructured":"Lee DA, Lee HJ, Park KM. Glymphatic dysfunction in isolated REM sleep behavior disorder. Acta Neurologica Scandinavica. 2022; 145: 464\u2013470.","DOI":"10.1111\/ane.13573"},{"key":"ref76","doi-asserted-by":"crossref","unstructured":"Si X, Guo T, Wang Z, Fang Y, Gu L, Cao L, et al. Neuroimaging evidence of glymphatic system dysfunction in possible REM sleep behavior disorder and Parkinson\u2019s disease. NPJ Parkinson\u2019s disease. 2022; 8: 54.","DOI":"10.1038\/s41531-022-00316-9"},{"key":"ref77","doi-asserted-by":"crossref","unstructured":"Bae YJ, Kim JM, Choi BS, Ryoo N, Song YS, Nam Y, et al. Altered Brain Glymphatic Flow at Diffusion-Tensor MRI in Rapid Eye Movement Sleep Behavior Disorder. Radiology. 2023; 307: e221848.","DOI":"10.1148\/radiol.221848"},{"key":"ref78","doi-asserted-by":"crossref","unstructured":"Wang Z, Song Z, Zhou C, Fang Y, Gu L, Yang W, et al. Reduced coupling of global brain function and cerebrospinal fluid dynamics in Parkinson\u2019s disease. Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism. 2023; 43: 1328\u20131339.","DOI":"10.1177\/0271678X231164337"},{"key":"ref79","doi-asserted-by":"crossref","unstructured":"Shen L. Gut, oral and nasal microbiota and Parkinson\u2019s disease. Microbial Cell Factories. 2020; 19: 50.","DOI":"10.1186\/s12934-020-01313-4"},{"key":"ref80","doi-asserted-by":"crossref","unstructured":"Heintz-Buschart A, Pandey U, Wicke T, Sixel-D\u00f6ring F, Janzen A, Sittig-Wiegand E, et al. The nasal and gut microbiome in Parkinson\u2019s disease and idiopathic rapid eye movement sleep behavior disorder. Movement Disorders: Official Journal of the Movement Disorder Society. 2018; 33: 88\u201398.","DOI":"10.1002\/mds.27105"},{"key":"ref81","doi-asserted-by":"crossref","unstructured":"Huang B, Chau SWH, Liu Y, Chan JWY, Wang J, Ma SL, et al. Gut microbiome dysbiosis across early Parkinson\u2019s disease, REM sleep behavior disorder and their first-degree relatives. Nature Communications. 2023; 14: 2501.","DOI":"10.1038\/s41467-023-38248-4"},{"key":"ref82","doi-asserted-by":"crossref","unstructured":"Ryman S, Vakhtin AA, Richardson SP, Lin HC. Microbiome-gut-brain dysfunction in prodromal and symptomatic Lewy body diseases. Journal of Neurology. 2023; 270: 746\u2013758.","DOI":"10.1007\/s00415-022-11461-9"},{"key":"ref83","doi-asserted-by":"crossref","unstructured":"Sweeney MD, Zhao Z, Montagne A, Nelson AR, Zlokovic BV. Blood-Brain Barrier: From Physiology to Disease and Back. Physiological Reviews. 2019; 99: 21\u201378.","DOI":"10.1152\/physrev.00050.2017"},{"key":"ref84","doi-asserted-by":"crossref","unstructured":"Forsythe P, Kunze WA. Voices from within: gut microbes and the CNS. Cellular and Molecular Life Sciences: CMLS. 2013; 70: 55\u201369.","DOI":"10.1007\/s00018-012-1028-z"},{"key":"ref85","doi-asserted-by":"crossref","unstructured":"Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, et al. Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson\u2019s disease. Cell. 2016; 167: 1469\u20131480.e12.","DOI":"10.1016\/j.cell.2016.11.018"},{"key":"ref86","doi-asserted-by":"crossref","unstructured":"Zhang X, Tang B, Guo J. Parkinson\u2019s disease and gut microbiota: from clinical to mechanistic and therapeutic studies. Translational Neurodegeneration. 2023; 12: 59.","DOI":"10.1186\/s40035-023-00392-8"},{"key":"ref87","doi-asserted-by":"crossref","unstructured":"Zhang P, Huang P, Li Y, Du J, Luo N, He Y, et al. Relationships Between Rapid Eye Movement Sleep Behavior Disorder and Parkinson\u2019s disease: Indication from Gut Microbiota Alterations. 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