Serum MicroRNAs Predict Isolated Rapid Eye Movement Sleep Behavior Disorder and Lewy Body Diseases. Issue 10 (12th August 2022)

• Record Type: Journal Article
• Authors: Soto, Marta; Iranzo, Alex; Lahoz, Sara; Fernández, Manel; Serradell, Mónica; Gaig, Carles; Melón, Paula; Martí, Maria‐Jose; Santamaría, Joan; Camps, Jordi; Fernández‐Santiago, Rubén; Ezquerra, Mario
• Is Part Of: Movement disorders. Volume 37:Issue 10(2022)
• Page Start: 2086
• Page End: 2098
• Publication Date: 2022-08-12
• Subjects: isolated REM‐sleep behavior disorder (IRBD) -- dopamine transporter single‐photon emission computed tomography (DaT‐SPECT) -- biomarkers -- disease prediction -- Parkinson's disease (PD); Movement disorders -- Periodicals; 610
• DOI: 10.1002/mds.29171
• Languages: English
• ISSNs: 0885-3185

Abstract

ABSTRACT: 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