Dataset Information

VCP expression decrease as a biomarker of preclinical and early clinical stages of Parkinson's disease.

ABSTRACT: Valosin-containing human protein (VCP) or p97 performs enzyme functions associated with the maintenance of protein homeostasis and control of protein quality. Disruption of its normal functioning might be associated with the development of Parkinson's disease (PD). Tissues of mice with toxin-induced presymptomatic and early symptomatic stages of PD, as well as 52 treated and untreated patients with newly diagnosed PD and nine patients with a "predicted" form of PD, were investigated. Significant changes in Vcp gene expression were observed in almost all studied mouse tissues. A significant decrease in VCP expression specific for PD was also detected at both the late preclinical and the early clinical stages of PD in untreated patients. Thus, a decrease in VCP expression is important for changes in the function of the nervous system at early stages of PD. Analysis of changes in VCP expression in all patients with PD and in Vcp in the peripheral blood of mice used as models of PD revealed significant decreases in expression specific for PD. These data suggest that a decrease in the relative levels of VCP mRNA might serve as a biomarker for the development of pathology at the early clinical and preclinical stages of human PD.

SUBMITTER: Alieva A

PROVIDER: S-EPMC6972783 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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VCP expression decrease as a biomarker of preclinical and early clinical stages of Parkinson's disease.

Alieva Anelya A Rudenok Margarita M Filatova Elena E Karabanov Alexey A Doronina Olga O Doronina Kseniya K Kolacheva Anna A Ugrumov Mikhail M Illarioshkin Sergey S Slominsky Petr P Shadrina Maria M

Scientific reports 20200121 1

Valosin-containing human protein (VCP) or p97 performs enzyme functions associated with the maintenance of protein homeostasis and control of protein quality. Disruption of its normal functioning might be associated with the development of Parkinson's disease (PD). Tissues of mice with toxin-induced presymptomatic and early symptomatic stages of PD, as well as 52 treated and untreated patients with newly diagnosed PD and nine patients with a "predicted" form of PD, were investigated. Significant ...[more]

PMID: 31964996

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Project description:Background:Different oscillations of brain networks could carry different dimensions of brain integration. We aimed to investigate oscillation-specific nodal alterations in patients with Parkinson's disease (PD) across early stage to middle stage by using graph theory-based analysis. Methods:Eighty-eight PD patients including 39 PD patients in the early stage (EPD) and 49 patients in the middle stage (MPD) and 36 controls were recruited in the present study. Graph theory-based network analyses from three oscillation frequencies (slow-5: 0.01-0.027?Hz; slow-4: 0.027-0.073?Hz; slow-3: 0.073-0.198?Hz) were analyzed. Nodal metrics (e.g. nodal degree centrality, betweenness centrality and nodal efficiency) were calculated. Results:Our results showed that (1) a divergent effect of oscillation frequencies on nodal metrics, especially on nodal degree centrality and nodal efficiency, that the anteroventral neocortex and subcortex had high nodal metrics within low oscillation frequencies while the posterolateral neocortex had high values within the relative high oscillation frequency was observed, which visually showed that network was perturbed in PD; (2) PD patients in early stage relatively preserved nodal properties while MPD patients showed widespread abnormalities, which was consistently detected within all three oscillation frequencies; (3) the involvement of basal ganglia could be specifically observed within slow-5 oscillation frequency in MPD patients; (4) logistic regression and receiver operating characteristic curve analyses demonstrated that some of those oscillation-specific nodal alterations had the ability to well discriminate PD patients from controls or MPD from EPD patients at the individual level; (5) occipital disruption within high frequency (slow-3) made a significant influence on motor impairment which was dominated by akinesia and rigidity. Conclusions:Coupling various oscillations could provide potentially useful information for large-scale network and progressive oscillation-specific nodal alterations were observed in PD patients across early to middle stages.

Project description:The identification of reliable biomarkers for early diagnosis and progression tracking of neurodegenerative diseases has become an important objective in clinical neuroscience in the last years. The P3a event-related potential, considered as the neurophysiological hallmark of novelty detection, has been shown to be reduced in Parkinson's disease (PD) and proposed as a sensitive measure for illness duration and severity. Our aim for this study was to explore for the first time whether impaired novelty detection could be observed through phase- and time-locked brain oscillatory activity at early PD. Twenty-seven patients with idiopathic PD at early stages (disease duration <5 years and Hoehn and Yahr stage <3) were included. A healthy control group (n = 24) was included as well. All participants performed an auditory involuntary attention task including frequent and deviant tones while a digital EEG was obtained. A neuropsychological battery was administered as well. Time-frequency representations of power and phase-locked oscillations and P3a amplitudes were compared between groups. We found a significant reduction of power and phase locking of slow oscillations (3-7 Hz) for deviant tones in the PD group compared to controls in the P3a time range (300-550 ms). Also, reduced modulation of late induced (not phase locked) alpha-beta oscillations (400-650 ms, 8-25 Hz) was observed in the PD group after deviant tones onset. The P3a amplitude was predicted by years of evolution in the PD group. Finally, while phase-locked slow oscillations were associated with task behavioral distraction effects, induced alpha-beta activity was related to cognitive flexibility performance. Our results show that novelty detection impairment can be identified in neurophysiological terms from very early stages of PD, and such impairment increases linearly as the disease progresses. Also, induced alpha-beta oscillations underlying novelty detection are related to executive functioning.

Dataset Information

VCP expression decrease as a biomarker of preclinical and early clinical stages of Parkinson's disease.

Publications

VCP expression decrease as a biomarker of preclinical and early clinical stages of Parkinson's disease.

Similar Datasets

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