Evaluation of Serum Apolipoprotein E as a Potential Biomarker for Pharmacological Therapeutic Efficacy Monitoring in Dopamine Dictated Disease Spectrum of Schizophrenia and Parkinson's disease: A Preliminary Study

Abstract

Aim of the study: Parkinson's disease and schizophrenia are disease end points of dopaminergic deficit and hyperactivity, respectively, in the mid brain. Accordingly, current medications aim to restore normal dopamine levels, overshooting of which results in adverse effects of psychosis and extra-pyramidal symptoms, respectively. There are currently no available laboratory tests to guide treatment decisions or help predict adverse side effects of the drugs. The aim was to therefore explore the possibility of using apolipoprotein E as a biomarker to monitor pharmacological intervention in dopamine dictated states of Parkinson's disease and schizophrenia for optimum therapy.

Methods: Naïve and treated, Parkinson's disease and schizophrenic patients were recruited from neurology and psychiatry clinics. Serum of healthy volunteers was collected as controls. Serum concentrations of apolipoprotein E was estimated by enzyme-linked immunosorbent assay (ELISA). Pathway analysis was carried out to delineate the interactions of apolipoprotein E in Parkinson's disease and schizophrenia.

Results: Apolipoprotein E levels are higher in Parkinson's disease patients as compared with schizophrenic samples (P < .05). Also, post-treatment apolipoprotein E levels in both disease states were at par with levels seen in healthy controls. The interactions of apolipoprotein E validate the results and place the differential expression of the protein in Parkinson's disease and schizophrenia in the right perspective.

Conclusion: Apolipoprotein E concentration across the dopaminergic spectrum suggests that it can be pursued not only as a potential biomarker in schizophrenia and Parkinson's disease, but can also be an effective tool for clinicians to determine efficacy of drug-based therapy.

Keywords: Parkinson’s disease; apolipoprotein E; dopamine; drug side effects; schizophrenia; therapeutic biomarker.

Figure 1.

Scatter plot showing the levels of apolipoprotein E (mean ± SD) in serum. The concentrations plotted are the average of duplicate readings of each sample. Diagrammatic representation of the dopamine concentration in cerebrospinal fluid is shown along the x-axis.^, Kruskal-Wallis non-parametric test was performed. * indicates P < .05.

Figure 2.

Pathway analysis shows apolipoprotein E along with its respective interactions in Parkinson’s disease and schizophrenia pathway. Apolipoprotein E is shown in white node, its interacting nodes in Parkinson’s disease pathway are highlighted in green, interacting nodes in schizophrenia pathway are highlighted in pink, and nodes that are common to both the pathways are in blue colour. First node interactions are shown circled by bold lines; and interactions from there on are shown circled by normal lines. Interactions that are connecting the nodes are shown by grey lines.

Figure 3.

Diagrammatic representation of neuronal synapse depicting experimental result-based hypothesis that explain molecular events in Parkinson’s disease, neurological controls, and schizophrenia. HSPG indicates heparan sulphate proteoglycan; L-DOPA, levodopa ; LRP, low-density lipid receptor protein; TLR2, toll-like receptor 2.