Novel biomarker signatures for idiopathic REM sleep behavior disorder

Abstract

ObjectiveTo perform a rigorous in-depth proteomics analysis to identify circulating biomarker signatures for idiopathic REM sleep behavior disorder (RBD), capable of providing new insights into the underlying pathogenic mechanisms and putative α-synuclein-related neurodegenerative processes.MethodsSerum samples from patients with idiopathic RBD (n = 9) and healthy controls (n = 10) were subjected to a thorough liquid chromatography–mass spectrometry (MS)/MS proteomics analysis using ultimate 3,000 nanoLC interfaced to an ESI-orbitrap velos. Data were analyzed with a systems biology approach to identify altered pathways in RBD.ResultsWe identified 259 proteins, 11 of which displayed significantly altered expression level in patients with RBD as compared to controls. Significant reduction in serum levels of dopamine β-hydroxylase (DBH) and vitamin D binding protein (GC) were consistent with alterations in the norepinephrinergic (NErgic) and dopaminergic systems, respectively. Additional altered protein profiles indicated that immunity, inflammation, complement, and coagulation also play a role in RBD pathophysiology.ConclusionsOur results shed light on the protein signature profile, molecular pathways, and mechanisms involved in the pathogenesis of RBD and its clinical manifestation. This knowledge opens a new avenue towards more accurate and timely diagnosis and characterization of RBD, which might ultimately translate into new therapeutic strategies with disease-modifying effects. Further evaluation of the identified markers is required to confirm their diagnostic value and potential to guide clinical decision-making.

Human blood serum proteome changes after 6 hours of sleep deprivation at night

“…This corresponds to other studies after sleep deprivation (Becker et al, 2014;Liu et al, 2009). This protein has also been shown in a novel proteomic study in idiopathic REM sleep behavior disorder to be differentially expressed (Mondello et al, 2018). It has been indicated to play a crucial role in regulating important physiological functions including complement activation, blood coagulation (FXIIa inhibitor), fibrinolysis and the generation of kinins.…”

“…PTPRG is a signaling molecule regarding cellular processes including differentiation, mitotic cycle, and oncogenic transformation (Cheung et al, 2015). This protein has been shown in a novel proteomic study in idiopathic REM sleep disorder to be differentially expressed (Mondello et al, 2018). A reduction in PTPRG might have a function in negative regulation of neuronal projection (Baker et al, 2000).…”

Peripheral Blood Inflammatory Cytokines in Idiopathic REM Sleep Behavior Disorder

“…However, this finding may simply reflect compensation against certain types of inflammatory processes, such as α‐synuclein accumulation. In contrast to our findings, a recent study showed that serum C‐reactive protein, which is another proinflammatory marker, was significantly upregulated in iRBD patients compared to healthy controls . However, this result was obtained from only 9 iRBD patients, and thus firm conclusions cannot be drawn.…”

Ten Unsolved Questions About Neuroinflammation in Parkinson's Disease

“…In line with this, inflammatory biomarkers were recently examined in studies of Rapid Eye Movement (REM) Behavior Disorder (RBD) patients. 75,76 There is some circumstantial evidence from studies of blood cytokines, which suggest that these are higher in early disease and decline with time, 77 as well as some evidence that blood lymphocytes recognizing α-synuclein antigens can be detected early. Stokholm et al 78 have observed increased PK 11195 binding in subjects with RBD.…”