Abstract
Depression is a common comorbidity in Parkinson's disease (PD) but is underdiagnosed. We aim to investigate the altered metabolic pathways of Parkinson's disease-related depression (PDD) in plasma and to identify potential biomarkers for clinical diagnosis. Consecutive patients with PD were recruited, clinically assessed, and patients with PDD identified. Fasting plasma samples were collected from 99 patients and differentially expressed metabolites and proteins between patients with PDD and PD were identified using non-targeted liquid chromatography-mass spectrometry (LC-MS)-based metabolomics and tandem mass tag (TMT)-based proteomics analysis, followed by an integrated analysis. Based on the above results, enzyme-linked immune sorbent assay (ELISA) tests were then performed to identify potential biomarkers for PDD. In clinics, patients with PDD suffered less hypertension and had lower serum low-density lipoprotein cholesterol and apolipoprotein B levels when compared to the other patients with PD. A total of 85 differentially expressed metabolites were identified in metabolomics analysis. These metabolites were mainly lipids and lipid-like molecules, involved in lipid and glucose metabolic pathways. According to proteomics analysis, 17 differentially expressed proteins were identified, and 12 metabolic pathways were enriched, which were predominantly related to glucose metabolism. Integrated analysis indicated that altered lipid and glucose metabolism in PDD may induce cellular injury through oxidative stress. Additionally, plasma levels of several proteins were confirmed to be significantly altered and correlated with depressive severity. NOTCH2 may be a potential blood biomarker for PDD, with an optimal cut-off point of 0.91 ng/ml, a sensitivity value of 95.65%, and a specificity value of 81.58%. Depressive symptoms are associated with lipid and glucose metabolism in patients with PD and NOTCH2 may be a potential blood biomarker for the clinical diagnosis of PDD.
Highlights
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease following Alzheimer’s disease, afflicting about 3.15% of people over 40 years old (Pringsheim et al, 2014)
One hundred and ten consecutively recruited patients with PD were included in the Department of Neurology, the First Affiliated Hospital of Chongqing Medical University from April 2016 to February 2017 in accordance with the following inclusion criteria: (i) Parkinson’s disease diagnosed according to the recommendation from the European Federation of Neurological Societies (EFNS) and the International Parkinson Movement Disorder Society’s European Section (MDS-ES) (Berardelli et al, 2013); (ii) Patients not treated with any drugs other than dopamine analogs or dopamine receptor agonists
Depressive symptoms were present in 23 patients (23.2%), which was approximately equal to the reported 17% in the literature (Reijnders et al, 2008)
Summary
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease following Alzheimer’s disease, afflicting about 3.15% of people over 40 years old (Pringsheim et al, 2014). Various studies have been conducted to identify diagnostic biomarkers (Sharma et al, 2013), the clinical diagnosis of patients with PD has been primarily based on cardinal motor features, including resting tremor, bradykinesia, and rigidity (Postuma et al, 2015) Nonmotor symptoms, such as constipation (Adams-Carr et al, 2016), hyposmia (Ponsen et al, 2009), rapid eye movement behavior disorder, cognition (Aarsland et al, 2005), anxiety (Broen et al, 2016), and depression (Reijnders et al, 2008) are reportedly more prevalent in patients with PD. Those nonmotor symptoms are often more problematic and distressing than the cardinal motor symptoms
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
