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.

Recent Evidence in Epigenomics and Proteomics Biomarkers for Early and Minimally Invasive Diagnosis of Alzheimer’s and Parkinson’s Diseases

“…Most of the proteomics studies in PD are focused on differential expression between PD and HC [ 147 , 237 - 244 ]. Few of them included early PD patients [ 245 – 247 ], while other studies included acute cerebral infarction [ 248 ] or schizophrenia [ 249 ], trying to differentiate these diseases from PD. Proteomic studies carried out in PD used predominantly serum samples (Table 2 ).…”

“…However, in spite of the fact that MAO-B may be useful in distinguishing AD from non-demented PD and healthy individuals, its levels were similar between AD and demented PD patients [ 170 ]. Also, PD could be differentiated from schizophrenic patients by means of serum ApoE levels [ 249 ]. Meanwhile, oxidized DJ-1 protein allowed a differential diagnosis for PD [ 258 ].…”

“…However, GFAP and NfL levels were higher in PD compared to HC, but they did not allow differentiation from acute cerebral infarction [ 248 ]. In the same sense, ApoE levels could discriminate PD from schizophrenia [ 249 ].…”

<p>Cerebrospinal Fluid Proteomics For Identification Of α2-Macroglobulin As A Potential Biomarker To Monitor Pharmacological Therapeutic Efficacy In Dopamine Dictated Disease States Of Parkinson’s Disease And Schizophrenia</p>

“…Potential biomarkers have been discovered in cerebrospinal fluid (CSF) using gel-based proteomic experiments for neurological diseases such as tubercular meningitis and Alzheimer’s disease 12,13. In our previous studies, we have highlighted the prospects of identifying protein biomarkers in serum and CSF to monitor the pharmaco-therapy of Parkinson’s disease and schizophrenia 14–16. In this study, we seek to identify potential biomarkers that are differentially expressed in the CSF across the dopaminergic-deficient state of Parkinson’s disease, the normal dopaminergic state, and the dopaminergic excess state of schizophrenia using isobaric Tag for Relative and Absolute Quantitation (iTRAQ).…”

<p>2D-DIGE as a strategy to identify serum protein biomarkers to monitor pharmacological efficacy in dopamine-dictated states of Parkinson&rsquo;s disease and schizophrenia</p>

“…While there have been a number of protein biomarkers for diagnosis or prognosis of Parkinson’s disease and schizophrenia, there has been no study to develop protein biomarkers to monitor drug therapy in these two diseases 35–39. In the recent past, our group has been looking into this aspect to provide valuable inputs in terms of protein biomarkers to monitor Parkinson’s disease and schizophrenia therapies 40,41. This makes a search for a reliable biomarker tool, which can assess the effectiveness of treatment responses and optimize pharmacological interventions in Parkinson’s disease and schizophrenia, very important and highly relevant.…”