Serum MicroRNAs Predict Isolated Rapid Eye Movement Sleep Behavior Disorder and Lewy Body Diseases.
Parkinson's disease (PD)
biomarkers
disease prediction
dopamine transporter single-photon emission computed tomography (DaT-SPECT)
isolated REM-sleep behavior disorder (IRBD)
Journal
Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
revised:
09
06
2022
received:
24
02
2022
accepted:
10
07
2022
pubmed:
14
8
2022
medline:
19
10
2022
entrez:
13
8
2022
Statut:
ppublish
Résumé
Isolated rapid eye movement sleep behavior disorder (IRBD) is a well-established clinical risk factor for Lewy body diseases (LBDs), such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB). To elucidate whether serum microRNA (miRNA) deregulation in IRBD can antedate the diagnosis of LBD by performing a longitudinal study in different progression stages of IRBD before and after LBD diagnosis and assessing the predictive performance of differentially expressed miRNAs by machine learning-based modeling. Using genome-wide miRNA analysis and real-time quantitative polymerase chain reaction validation, we assessed serum miRNA profiles from patients with IRBD stratified by dopamine transporter (DaT) single-photon emission computed tomography into DaT-negative IRBD (n = 17) and DaT-positive IRBD (n = 21), IRBD phenoconverted into LBD (n = 13), and controls (n = 20). Longitudinally, we followed up the IRBD cohort by studying three time point serum samples over 26 months. We found sustained cross-sectional and longitudinal deregulation of 12 miRNAs across the RBD continuum, including DaT-negative IRBD, DaT-positive IRBD, and LBD phenoconverted IRBD (let-7c-5p, miR-19b-3p, miR-140, miR-22-3p, miR-221-3p, miR-24-3p, miR-25-3p, miR-29c-3p, miR-361-5p, miR-425-5p, miR-4505, and miR-451a) (false discovery rate P < 0.05). Age- and sex-adjusted predictive modeling based on the 12 differentially expressed miRNA biosignatures discriminated IRBD and PD or DLB from controls with an area under the curve of 98% (95% confidence interval: 89-99%). Besides clinical diagnosis of IRBD or imaging markers such as DaT single-photon emission computed tomography, specific miRNA biosignatures alone hold promise as progression biomarkers for patients with IRBD for predicting PD and DLB clinical outcomes. Further miRNA studies in other PD at-risk populations, such as LRRK2 mutation asymptomatic carriers or hyposmic subjects, are warranted. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Sections du résumé
BACKGROUND
Isolated rapid eye movement sleep behavior disorder (IRBD) is a well-established clinical risk factor for Lewy body diseases (LBDs), such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB).
OBJECTIVE
To elucidate whether serum microRNA (miRNA) deregulation in IRBD can antedate the diagnosis of LBD by performing a longitudinal study in different progression stages of IRBD before and after LBD diagnosis and assessing the predictive performance of differentially expressed miRNAs by machine learning-based modeling.
METHODS
Using genome-wide miRNA analysis and real-time quantitative polymerase chain reaction validation, we assessed serum miRNA profiles from patients with IRBD stratified by dopamine transporter (DaT) single-photon emission computed tomography into DaT-negative IRBD (n = 17) and DaT-positive IRBD (n = 21), IRBD phenoconverted into LBD (n = 13), and controls (n = 20). Longitudinally, we followed up the IRBD cohort by studying three time point serum samples over 26 months.
RESULTS
We found sustained cross-sectional and longitudinal deregulation of 12 miRNAs across the RBD continuum, including DaT-negative IRBD, DaT-positive IRBD, and LBD phenoconverted IRBD (let-7c-5p, miR-19b-3p, miR-140, miR-22-3p, miR-221-3p, miR-24-3p, miR-25-3p, miR-29c-3p, miR-361-5p, miR-425-5p, miR-4505, and miR-451a) (false discovery rate P < 0.05). Age- and sex-adjusted predictive modeling based on the 12 differentially expressed miRNA biosignatures discriminated IRBD and PD or DLB from controls with an area under the curve of 98% (95% confidence interval: 89-99%).
CONCLUSIONS
Besides clinical diagnosis of IRBD or imaging markers such as DaT single-photon emission computed tomography, specific miRNA biosignatures alone hold promise as progression biomarkers for patients with IRBD for predicting PD and DLB clinical outcomes. Further miRNA studies in other PD at-risk populations, such as LRRK2 mutation asymptomatic carriers or hyposmic subjects, are warranted. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Identifiants
pubmed: 35962561
doi: 10.1002/mds.29171
pmc: PMC9804841
doi:
Substances chimiques
Biomarkers
0
Dopamine Plasma Membrane Transport Proteins
0
MicroRNAs
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2086-2098Informations de copyright
© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Références
Oncotarget. 2018 Apr 3;9(25):17455-17465
pubmed: 29707120
Neurology. 2017 Apr 11;88(15):1461-1467
pubmed: 28283599
Mov Disord. 2020 Oct;35(10):1873-1879
pubmed: 32687224
Brief Bioinform. 2016 Mar;17(2):204-12
pubmed: 26238539
Nat Aging. 2021 Mar;1(3):309-322
pubmed: 37118411
Neurology. 2020 Sep 1;95(9):e1267-e1284
pubmed: 32747521
Cell Mol Life Sci. 2019 Sep;76(18):3497-3514
pubmed: 31089747
Cell. 2004 Jan 23;116(2):281-97
pubmed: 14744438
Cancer Res. 2004 Aug 1;64(15):5245-50
pubmed: 15289330
J Alzheimers Dis Parkinsonism. 2012 Aug;2(3):
pubmed: 23024925
J Mol Neurosci. 2014 Dec;54(4):830-6
pubmed: 25284245
Clin Chem. 2015 Nov;61(11):1333-42
pubmed: 26408530
J Neurosci Res. 2014 Aug;92(8):1071-7
pubmed: 24648008
Microarrays (Basel). 2013 Mar 14;2(1):24-33
pubmed: 27605179
Brain Behav. 2018 Feb 19;8(4):e00941
pubmed: 29670823
J Biotechnol. 2011 Mar 20;152(3):96-101
pubmed: 21295623
Mov Disord. 2017 Feb;32(2):219-226
pubmed: 28090684
Mov Disord. 2007 Jul 15;22(9):1229-38
pubmed: 17486648
Lancet Neurol. 2021 Mar;20(3):203-212
pubmed: 33609478
Mov Disord. 2019 Sep;34(9):1354-1364
pubmed: 31361367
Cell Biochem Funct. 2016 Oct;34(7):511-515
pubmed: 27748571
Mol Neurobiol. 2017 Dec;54(10):7736-7745
pubmed: 27844283
Neurosci Lett. 2017 Mar 22;644:94-99
pubmed: 28223160
Ann Neurol. 2019 Jun;85(6):835-851
pubmed: 30990912
Lancet Neurol. 2013 May;12(5):443-53
pubmed: 23562390
Front Mol Neurosci. 2016 Aug 17;9:69
pubmed: 27582688
RNA Biol. 2018 Feb 1;15(2):242-250
pubmed: 29219730
Oncogene. 2003 Nov 24;22(53):8628-33
pubmed: 14634624
Front Neurosci. 2020 Aug 18;14:848
pubmed: 33013286
Neurobiol Aging. 2016 Feb;38:214.e1-214.e5
pubmed: 26675812
Parkinsonism Relat Disord. 2016 Dec;33:115-121
pubmed: 27717584
Sci Rep. 2017 Jul 14;7(1):5411
pubmed: 28710399
Sci Rep. 2019 Sep 24;9(1):13759
pubmed: 31551498
PLoS One. 2011;6(10):e25443
pubmed: 22003392
Mov Disord. 2015 Oct;30(12):1591-601
pubmed: 26474316
Nucleic Acids Res. 2005 Nov 27;33(20):e179
pubmed: 16314309
J Neurol Neurosurg Psychiatry. 2020 Jul;91(7):720-729
pubmed: 32273329
Ann Neurol. 2015 May;77(5):895-901
pubmed: 25675938
Neurology. 2005 Dec 27;65(12):1863-72
pubmed: 16237129
Biomedicines. 2021 Sep 20;9(9):
pubmed: 34572457
Brain Res. 2015 Aug 27;1618:111-21
pubmed: 26047984
Front Cell Neurosci. 2014 Jun 10;8:156
pubmed: 24959119
Neurosci Lett. 2016 Aug 26;629:99-104
pubmed: 27369327
Oncotarget. 2015 Nov 10;6(35):37043-53
pubmed: 26497684
J Neurol Neurosurg Psychiatry. 2010 Jan;81(1):5-12
pubmed: 20019219
Biochem Biophys Res Commun. 2017 Mar 11;484(3):557-564
pubmed: 28131841
Nucleic Acids Res. 2020 Jul 2;48(W1):W521-W528
pubmed: 32374865
Sleep. 2018 Aug 1;41(8):
pubmed: 29790977
FASEB J. 2020 Oct;34(10):14042-14054
pubmed: 32910484
Front Mol Neurosci. 2020 Mar 19;13:38
pubmed: 32265650
J Neurol Neurosurg Psychiatry. 2010 Sep;81(9):1008-13
pubmed: 20562452
Parkinsonism Relat Disord. 2016 Jan;22:68-73
pubmed: 26631952
Front Cell Neurosci. 2013 Dec 19;7:265
pubmed: 24391543
Ann Neurol. 2017 Sep;82(3):419-428
pubmed: 28833467
Trends Biochem Sci. 2012 Nov;37(11):460-5
pubmed: 22944280