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Evaluation of α-synuclein and apolipoprotein E as potential biomarkers in cerebrospinal fluid to monitor pharmacotherapeutic efficacy in dopamine dictated disease states of Parkinson’s disease and schizophrenia
BACKGROUND AND OBJECTIVE: Dopamine plays an important role in the disease pathology of Parkinson’s disease and schizophrenia. These two neuropsychiatric disorders represent disease end points of the dopaminergic spectrum where Parkinson’s disease represents dopamine deficit and schizophrenia represe...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650621/ https://www.ncbi.nlm.nih.gov/pubmed/31410011 http://dx.doi.org/10.2147/NDT.S205550 |
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author | Gupta, Ashish Kumar Pokhriyal, Ruchika Das, Uddipan Khan, Mohd Imran Ratna Kumar, Domada Gupta, Rishab Chadda, Rakesh Kumar Ramachandran, Rashmi Goyal, Vinay Tripathi, Manjari Hariprasad, Gururao |
author_facet | Gupta, Ashish Kumar Pokhriyal, Ruchika Das, Uddipan Khan, Mohd Imran Ratna Kumar, Domada Gupta, Rishab Chadda, Rakesh Kumar Ramachandran, Rashmi Goyal, Vinay Tripathi, Manjari Hariprasad, Gururao |
author_sort | Gupta, Ashish Kumar |
collection | PubMed |
description | BACKGROUND AND OBJECTIVE: Dopamine plays an important role in the disease pathology of Parkinson’s disease and schizophrenia. These two neuropsychiatric disorders represent disease end points of the dopaminergic spectrum where Parkinson’s disease represents dopamine deficit and schizophrenia represents dopamine hyperactivity in the mid-brain. Therefore, current treatment strategies aim to restore normal dopamine levels. However, during treatment patients develop adverse effects due to overshooting of physiological levels of dopamine leading to psychosis in Parkinson’s disease, and extrapyramidal symptoms in schizophrenia. Absence of any laboratory tests hampers modulation of pharmacotherapy. Apolipoprotein E and α-synuclein have an important role in the neuropathology of these two diseases. The objective of this study was to evaluate cerebrospinal fluid (CSF) concentrations of apolipoprotein E and α-synuclein in patients with these two diseases so that they may serve as biomarkers to monitor therapy in Parkinson’s disease and schizophrenia. METHODS: Drug-naïve Parkinson’s disease patients and Parkinson’s disease patients treated with dopaminergic therapy, neurological controls, schizophrenic patients treated with antidopaminergic therapy, and drug-naïve schizophrenic patients were recruited for the study and CSF was collected. Enzyme-linked immunosorbent assays were carried out to estimate the concentrations of apolipoprotein E and α-synuclein. Pathway analysis was done to establish a possible role of these two proteins in various pathways in these two dopamine dictated diseases. RESULTS: Apolipoprotein E and α-synuclein CSF concentrations have an inverse correlation along the entire dopaminergic clinical spectrum. Pathway analysis convincingly establishes a plausible hypothesis for their co-regulation in the pathogenesis of Parkinson’s disease and schizophrenia. Each protein by itself or as a combination has encouraging sensitivity and specificity values of more than 55%. CONCLUSION: The dynamic variation of these two proteins along the spectrum is ideal for them to be pursued as pharmacotherapeutic biomarkers in CSF to monitor pharmacological efficacy in Parkinson’s disease and schizophrenia. |
format | Online Article Text |
id | pubmed-6650621 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-66506212019-08-13 Evaluation of α-synuclein and apolipoprotein E as potential biomarkers in cerebrospinal fluid to monitor pharmacotherapeutic efficacy in dopamine dictated disease states of Parkinson’s disease and schizophrenia Gupta, Ashish Kumar Pokhriyal, Ruchika Das, Uddipan Khan, Mohd Imran Ratna Kumar, Domada Gupta, Rishab Chadda, Rakesh Kumar Ramachandran, Rashmi Goyal, Vinay Tripathi, Manjari Hariprasad, Gururao Neuropsychiatr Dis Treat Original Research BACKGROUND AND OBJECTIVE: Dopamine plays an important role in the disease pathology of Parkinson’s disease and schizophrenia. These two neuropsychiatric disorders represent disease end points of the dopaminergic spectrum where Parkinson’s disease represents dopamine deficit and schizophrenia represents dopamine hyperactivity in the mid-brain. Therefore, current treatment strategies aim to restore normal dopamine levels. However, during treatment patients develop adverse effects due to overshooting of physiological levels of dopamine leading to psychosis in Parkinson’s disease, and extrapyramidal symptoms in schizophrenia. Absence of any laboratory tests hampers modulation of pharmacotherapy. Apolipoprotein E and α-synuclein have an important role in the neuropathology of these two diseases. The objective of this study was to evaluate cerebrospinal fluid (CSF) concentrations of apolipoprotein E and α-synuclein in patients with these two diseases so that they may serve as biomarkers to monitor therapy in Parkinson’s disease and schizophrenia. METHODS: Drug-naïve Parkinson’s disease patients and Parkinson’s disease patients treated with dopaminergic therapy, neurological controls, schizophrenic patients treated with antidopaminergic therapy, and drug-naïve schizophrenic patients were recruited for the study and CSF was collected. Enzyme-linked immunosorbent assays were carried out to estimate the concentrations of apolipoprotein E and α-synuclein. Pathway analysis was done to establish a possible role of these two proteins in various pathways in these two dopamine dictated diseases. RESULTS: Apolipoprotein E and α-synuclein CSF concentrations have an inverse correlation along the entire dopaminergic clinical spectrum. Pathway analysis convincingly establishes a plausible hypothesis for their co-regulation in the pathogenesis of Parkinson’s disease and schizophrenia. Each protein by itself or as a combination has encouraging sensitivity and specificity values of more than 55%. CONCLUSION: The dynamic variation of these two proteins along the spectrum is ideal for them to be pursued as pharmacotherapeutic biomarkers in CSF to monitor pharmacological efficacy in Parkinson’s disease and schizophrenia. Dove 2019-07-19 /pmc/articles/PMC6650621/ /pubmed/31410011 http://dx.doi.org/10.2147/NDT.S205550 Text en © 2019 Gupta et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Gupta, Ashish Kumar Pokhriyal, Ruchika Das, Uddipan Khan, Mohd Imran Ratna Kumar, Domada Gupta, Rishab Chadda, Rakesh Kumar Ramachandran, Rashmi Goyal, Vinay Tripathi, Manjari Hariprasad, Gururao Evaluation of α-synuclein and apolipoprotein E as potential biomarkers in cerebrospinal fluid to monitor pharmacotherapeutic efficacy in dopamine dictated disease states of Parkinson’s disease and schizophrenia |
title |
Evaluation of α-synuclein and apolipoprotein E as potential biomarkers in cerebrospinal fluid to monitor pharmacotherapeutic efficacy in dopamine dictated disease states of Parkinson’s disease and schizophrenia |
title_full |
Evaluation of α-synuclein and apolipoprotein E as potential biomarkers in cerebrospinal fluid to monitor pharmacotherapeutic efficacy in dopamine dictated disease states of Parkinson’s disease and schizophrenia |
title_fullStr |
Evaluation of α-synuclein and apolipoprotein E as potential biomarkers in cerebrospinal fluid to monitor pharmacotherapeutic efficacy in dopamine dictated disease states of Parkinson’s disease and schizophrenia |
title_full_unstemmed |
Evaluation of α-synuclein and apolipoprotein E as potential biomarkers in cerebrospinal fluid to monitor pharmacotherapeutic efficacy in dopamine dictated disease states of Parkinson’s disease and schizophrenia |
title_short |
Evaluation of α-synuclein and apolipoprotein E as potential biomarkers in cerebrospinal fluid to monitor pharmacotherapeutic efficacy in dopamine dictated disease states of Parkinson’s disease and schizophrenia |
title_sort | evaluation of α-synuclein and apolipoprotein e as potential biomarkers in cerebrospinal fluid to monitor pharmacotherapeutic efficacy in dopamine dictated disease states of parkinson’s disease and schizophrenia |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650621/ https://www.ncbi.nlm.nih.gov/pubmed/31410011 http://dx.doi.org/10.2147/NDT.S205550 |
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