Abstract
Parkinson’s disease (PD) is the second most common neurodegenerative disease clinically characterized by classical motor symptoms and a range of associated non-motor symptoms. Due to the heterogeneity of symptoms and variability in patient prognosis, the discovery of blood biomarkers is of utmost importance to identify the biological mechanisms underlying the different clinical manifestations of PD, monitor its progression and develop personalized treatment strategies. Whereas studies often rely on motor symptoms alone or composite scores, our study focused on finding relevant molecular markers associated with three clinical models describing either motor, cognitive or emotional symptoms. An integrative multiblock approach was performed using regularized generalized canonical correlation analysis to determine specific associations between lipidomics, transcriptomics and clinical data in 48 PD patients. We identified omics signatures confirming that clinical manifestations of PD in our cohort could be classified according to motor, cognition or emotion models. We found that immune-related genes and triglycerides were well-correlated with motor variables, while cognitive variables were linked to triglycerides as well as genes involved in neuronal growth, synaptic plasticity and mitochondrial fatty acid oxidation. Furthermore, emotion variables were associated with phosphatidylcholines, cholesteryl esters and genes related to endoplasmic reticulum stress and cell regulation.
Highlights
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases
We found an association between the omics and UPDRS-III OFF scores
We identified four genes (KRT23, leukotriene B4 receptor 2 (LTB4R2), KANK1 and SLC25A20) whose expression positively correlated with increasing UPDRS-III OFF scores and TMT B-A, but negatively correlated with MATTIS, To obtain a synthetic view of our analyses, we merged the clinical and omics components of the three clinical models into a “super-block”, combining all lipids and genes used to build the three clinical models (Figure 4)
Summary
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. It is characterized by a motor triad (rest tremor, akinesia, rigidity), which is largely improved by dopamine replacement therapy. We identified alterations of physiological (oculomotor and gait) and imaging parameters, which could be markers of sleep disorders [1,2], poorer gait and gaze control [2–4] and cognitive impairment [5]. These physiological assessments of gait or gaze, as well as MRI analysis of small deep structures and networks, require much expertise and technical facilities that are not yet readily available to patients
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