Detection of a Parkinson's Disease–Specific MicroRNA Signature in Nasal and Oral Swabs

BACKGROUND Biomaterials from oral and nasal swabs provide, in theory, a potential resource for biomarker development. However, their diagnostic value has not yet been investigated in the context of Parkinson's disease (PD) and associated conditions. OBJECTIVE We have previously identified a PD-specific microRNA (miRNA) signature in gut biopsies. In this work, we aimed to investigate the expression of miRNAs in routine buccal (oral) and nasal swabs obtained from cases with idiopathic PD and isolated rapid eye movement sleep behavior disorder (iRBD), a prodromal symptom that often precedes α-synucleinopathies. We aimed to address their value as a diagnostic biomarker for PD and their mechanistic contribution to PD onset and progression. METHODS Healthy control cases (n = 28), cases with PD (n = 29), and cases with iRBD (n = 8) were prospectively recruited to undergo routine buccal and nasal swabs. Total RNA was extracted from the swab material, and the expression of a predefined set of miRNAs was quantified by quantitative real-time polymerase chain reaction. RESULTS Statistical analysis revealed a significantly increased expression of hsa-miR-1260a in cases who had PD. Interestingly, hsa-miR-1260a expression levels correlated with diseases severity, as well as olfactory function, in the PD and iRBD cohorts. Mechanistically, hsa-miR-1260a segregated to Golgi-associated cellular processes with a potential role in mucosal plasma cells. Predicted hsa-miR-1260a target gene expression was reduced in iRBD and PD groups. CONCLUSIONS Our work demonstrates oral and nasal swabs as a valuable biomarker pool in PD and associated neurodegenerative conditions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

[1]  C. Gaig,et al.  Misfolded α-Synuclein Assessment in the Skin and CSF by RT-QuIC in Isolated REM Sleep Behavior Disorder , 2023, Neurology.

[2]  F. Amati,et al.  Expression analysis of miRNA hsa‐let7b‐5p in naso‐oropharyngeal swabs of COVID‐19 patients supports its role in regulating ACE2 and DPP4 receptors , 2022, Journal of cellular and molecular medicine.

[3]  J. Santamaria,et al.  Serum MicroRNAs Predict Isolated Rapid Eye Movement Sleep Behavior Disorder and Lewy Body Diseases , 2022, Movement disorders : official journal of the Movement Disorder Society.

[4]  B. Mollenhauer,et al.  Evidence for immune system alterations in peripheral biological fluids in Parkinson's disease , 2022, Neurobiology of Disease.

[5]  E. Fedele,et al.  MicroRNA Alteration, Application as Biomarkers, and Therapeutic Approaches in Neurodegenerative Diseases , 2022, International journal of molecular sciences.

[6]  L. Bertram,et al.  Differential microRNA expression analyses across two brain regions in Alzheimer’s disease , 2022, bioRxiv.

[7]  C. Stewart,et al.  Detection of SARS-CoV-2 infection by microRNA profiling of the upper respiratory tract , 2021, PloS one.

[8]  M. Haniffa,et al.  Human oral mucosa cell atlas reveals a stromal-neutrophil axis regulating tissue immunity , 2021, Cell.

[9]  Verena E. Rozanski,et al.  Differential expression of gut miRNAs in idiopathic Parkinson's disease. , 2021, Parkinsonism & related disorders.

[10]  A. Ribeiro-dos-Santos,et al.  Regulatory miRNA–mRNA Networks in Parkinson’s Disease , 2021, Cells.

[11]  S. Fereshtehnejad,et al.  Prodromal Parkinson disease subtypes — key to understanding heterogeneity , 2021, Nature Reviews Neurology.

[12]  E. Tolosa,et al.  Alpha-synuclein seeds in olfactory mucosa of patients with isolated REM sleep behaviour disorder. , 2021, Brain : a journal of neurology.

[13]  V. Haroutunian,et al.  Streamlined alpha-synuclein RT-QuIC assay for various biospecimens in Parkinson’s disease and dementia with Lewy bodies , 2021, Acta neuropathologica communications.

[14]  N. Davoust,et al.  Spen modulates lipid droplet content in adult Drosophila glial cells and protects against paraquat toxicity , 2020, Scientific Reports.

[15]  Raphael Gottardo,et al.  Integrated analysis of multimodal single-cell data , 2020, Cell.

[16]  Jing Yang,et al.  Optimization of the Detection Method for Phosphorylated α-Synuclein in Parkinson Disease by Skin Biopsy , 2020, Frontiers in Neurology.

[17]  D. Brooks,et al.  Brain-first versus body-first Parkinson's disease: a multimodal imaging case-control study. , 2020, Brain : a journal of neurology.

[18]  Verena E. Rozanski,et al.  Analyzing the co-localization of substantia nigra hyper-echogenicities and iron accumulation in Parkinson's disease: A multi-modal atlas study with transcranial ultrasound and MRI , 2020, NeuroImage: Clinical.

[19]  Xiaowei Wang,et al.  miRDB: an online database for prediction of functional microRNA targets , 2019, Nucleic Acids Res..

[20]  S. Fereshtehnejad,et al.  Evolution of prodromal Parkinson's disease and dementia with Lewy bodies: a prospective study. , 2019, Brain : a journal of neurology.

[21]  Laura Verga,et al.  The risk of neurodegeneration in REM sleep behavior disorder: A systematic review and meta-analysis of longitudinal studies. , 2019, Sleep medicine reviews.

[22]  J. Jankovic,et al.  Safety and Tolerability of Multiple Ascending Doses of PRX002/RG7935, an Anti–&agr;-Synuclein Monoclonal Antibody, in Patients With Parkinson Disease: A Randomized Clinical Trial , 2018, JAMA neurology.

[23]  Yves Dauvilliers,et al.  REM sleep behaviour disorder , 2018, Nature Reviews Disease Primers.

[24]  J. Trojanowski,et al.  Measurements of auto‐antibodies to α‐synuclein in the serum and cerebral spinal fluids of patients with Parkinson's disease , 2018, Journal of neurochemistry.

[25]  Z. Mari,et al.  Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson’s disease , 2018, Nature Medicine.

[26]  C. Olanow,et al.  Do subjects with minimal motor features have prodromal Parkinson disease? , 2018, Annals of neurology.

[27]  A. Shalash,et al.  Elevated Serum α-Synuclein Autoantibodies in Patients with Parkinson’s Disease Relative to Alzheimer’s Disease and Controls , 2017, Front. Neurol..

[28]  J. Konkel,et al.  Tissue-Specific Immunity at the Oral Mucosal Barrier. , 2017, Trends in immunology.

[29]  H. Blankenburg,et al.  Plasma and White Blood Cells Show Different miRNA Expression Profiles in Parkinson’s Disease , 2017, Journal of Molecular Neuroscience.

[30]  H. Weiner,et al.  History and mechanisms of oral tolerance. , 2017, Seminars in immunology.

[31]  S. Factor,et al.  LRRK2 levels in immune cells are increased in Parkinson’s disease , 2017, npj Parkinson's Disease.

[32]  I. Horváth,et al.  Immunochemical Detection of α-Synuclein Autoantibodies in Parkinson's Disease: Correlation between Plasma and Cerebrospinal Fluid Levels. , 2017, ACS chemical neuroscience.

[33]  D. Vaillancourt,et al.  Subliminal gait initiation deficits in rapid eye movement sleep behavior disorder: A harbinger of freezing of gait? , 2016, Movement disorders : official journal of the Movement Disorder Society.

[34]  Daniela Berg,et al.  Advances in markers of prodromal Parkinson disease , 2016, Nature Reviews Neurology.

[35]  M. Esiri,et al.  Alpha‐synuclein RT‐QuIC in the CSF of patients with alpha‐synucleinopathies , 2016, Annals of clinical and translational neurology.

[36]  Andrew D. Rouillard,et al.  Enrichr: a comprehensive gene set enrichment analysis web server 2016 update , 2016, Nucleic Acids Res..

[37]  M. Kubo,et al.  Leucine-rich repeat kinase 2 is a regulator of B cell function, affecting homeostasis, BCR signaling, IgA production, and TI antigen responses , 2016, Journal of Neuroimmunology.

[38]  Nir Giladi,et al.  Down-regulation of B cell-related genes in peripheral blood leukocytes of Parkinson's disease patients with and without GBA mutations. , 2016, Molecular genetics and metabolism.

[39]  A. Sidhu,et al.  α-Synuclein-mediated inhibition of ATF6 processing into COPII vesicles disrupts UPR signaling in Parkinson's disease , 2015, Neurobiology of Disease.

[40]  J. Sainz,et al.  Identification of candidate genes for Parkinson's disease through blood transcriptome analysis in LRRK2-G2019S carriers, idiopathic cases, and controls , 2015, Neurobiology of Aging.

[41]  L. Bardram,et al.  GLP-1 receptor localization in monkey and human tissue: novel distribution revealed with extensively validated monoclonal antibody. , 2014, Endocrinology.

[42]  Xuemei Chen,et al.  MicroRNAs Inhibit the Translation of Target mRNAs on the Endoplasmic Reticulum in Arabidopsis , 2013, Cell.

[43]  L. Petrucelli,et al.  TARDBP mutations in Parkinson's disease. , 2013, Parkinsonism & related disorders.

[44]  G. Halliday,et al.  Reduced T helper and B lymphocytes in Parkinson's disease , 2012, Journal of Neuroimmunology.

[45]  A. Lang,et al.  How does parkinsonism start? Prodromal parkinsonism motor changes in idiopathic REM sleep behaviour disorder. , 2012, Brain : a journal of neurology.

[46]  W. Poewe,et al.  Defining at‐risk populations for Parkinson's disease: Lessons from ongoing studies , 2012, Movement disorders : official journal of the Movement Disorder Society.

[47]  Xiaowei Wang,et al.  PrimerBank: a PCR primer database for quantitative gene expression analysis, 2012 update , 2011, Nucleic Acids Res..

[48]  K. Yanamandra,et al.  Immunoprotection against toxic biomarkers is retained during Parkinson's disease progression , 2011, Journal of Neuroimmunology.

[49]  R. Postuma,et al.  Markers of neurodegeneration in idiopathic rapid eye movement sleep behaviour disorder and Parkinson's disease. , 2009, Brain : a journal of neurology.

[50]  R. Insall,et al.  WASP and SCAR/WAVE proteins: the drivers of actin assembly , 2009, Journal of Cell Science.

[51]  E. Hirsch,et al.  Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. , 2008, The Journal of clinical investigation.

[52]  H. Gendelman,et al.  Nitrated α–Synuclein Immunity Accelerates Degeneration of Nigral Dopaminergic Neurons , 2008, PloS one.

[53]  Geert Mayer,et al.  The REM sleep behavior disorder screening questionnaire—A new diagnostic instrument , 2007, Movement disorders : official journal of the Movement Disorder Society.

[54]  A. Bonnet,et al.  Motor score of the Unified Parkinson Disease Rating Scale as a good predictor of Lewy body-associated neuronal loss in the substantia nigra. , 2006, Archives of neurology.

[55]  G. Halliday,et al.  A possible role for humoral immunity in the pathogenesis of Parkinson's disease. , 2005, Brain : a journal of neurology.

[56]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[57]  S. Appel,et al.  Experimental destruction of substantia nigra initiated by Parkinson disease immunoglobulins. , 1998, Archives of neurology.

[58]  G Kobal,et al.  "Sniffin' sticks": screening of olfactory performance. , 1996, Rhinology.

[59]  A. Lees,et al.  Ageing and Parkinson's disease: substantia nigra regional selectivity. , 1991, Brain : a journal of neurology.

[60]  J. Gusella,et al.  Genomewide Association Study for Onset Age in Parkinson Disease , 2009 .

[61]  A. Zinsmeister,et al.  FUNCTIONAL BOWEL DISORDERS , 2007, The American Journal of Gastroenterology.

[62]  F. Walshe A Journal of Neurology , 2005 .