Expression of prion protein in the cerebrospinal fluid of patients with Parkinson’s disease complicated with rapid eye movement sleep behavior disorder

Abstract

ABSTRACT. Parkinson's disease (PD) is one of the most common neurodegenerative diseases and mainly manifests with decreasing numbers of dopaminergic neurons. Rapid eye movement (REM) sleep behavior disorder (RBD) has an incidence of 15-47% in all PD patients. Prion proteins (PrPs), which are expressed in both neurons and glial cells of the brain, are believed to be correlated with abnormal neurological functions, although their role in PD-related sleeping disorders remains unclear. We therefore investigated the expressional profiles of PrP in PD patients with RBD. Quantitative real-time polymerase chain reaction and western blotting were used to detect the mRNA and protein levels of PrP, respectively, in the cerebrospinal fluid (CSF) of PD patients with RBD, PD patients without sleeping disorder, and healthy people (N = 23 each). We investigated the correlation between the CSF PrP level and sleeping behavior in PD patients. Patients with PD complicated with RBD had significantly elevated CSF PrP expression levels (both mRNA and protein) compared with either PD patients without sleeping disorder or healthy individuals (P < 0.05 in both cases). There is elevated expression of PrP in the CSF of PD patients with RBD. This may benefit the diagnosis of PD-related RBD.

Longitudinal Alterations of Alpha-Synuclein, Amyloid Beta, Total, and Phosphorylated Tau in Cerebrospinal Fluid and Correlations Between Their Changes in Parkinson's Disease

“…In this study, we detected significant increase in CSF levels of alpha-synuclein in PD-RBD patients. Although a previous cross-sectional study in PD patients have revealed no association between CSF alpha-synuclein levels and RBD ( 46 ), prior investigations have revealed that CSF Prion Proteins (PrPs) are significantly elevated in PD patients with RBD compared to PD patients without sleep disorders ( 47 ), which might be suggestive of accelerated neuronal degeneration in PD-RBD patients and thus, introduce RBD as potentially the most appropriate clinical predictive marker of neuronal degeneration and disease progression in PD, as shown previously ( 48 ).…”

Predictors of RBD progression and conversion to synucleinopathies

“…A longitudinal study illustrated that lower baseline amyloid-β 42 levels were predictive of cognitive decline at three-year follow-up only in PD patients with RBD [92]. Increased CSF prion protein levels have also been reported in PD patients with RBD compared to PD patients without RBD [93]. CSF inflammatory markers, including interleukin 1β and nitric oxide, as well as serum prostaglandin E2 have also been shown to be elevated in PD patients with RBD [90].…”

Accuracy of Rating Scales and Clinical Measures for Screening of Rapid Eye Movement Sleep Behavior Disorder and for Predicting Conversion to Parkinson’s Disease and Other Synucleinopathies

“…Anderson et al, ( 121 ) found normal hypocretin levels in the CSF of RBD subjects. Elevated expression of prion protein (PrP, both mRNA and protein) in PD patients with RBD, compared to PD patients without sleep problems and healthy controls has been recently reported ( 122 ). Although total alpha-synuclein was reportedly lower in early untreated PD patients compared to healthy controls and CSF total tau was slightly higher, the rates of changes were not significant after 24 months of follow-up and, moreover, these CSF parameters were not studied in iRBD subjects specifically so far ( 123 ).…”