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CSF Biomarkers and Its Associations with (18)F-AV133 Cerebral VMAT2 Binding in Parkinson’s Disease—A Preliminary Report

OBJECTIVE: Cerebrospinal fluid (CSF) biomarkers, such as α-synuclein (α-syn), amyloid beta peptide 1–42 (Aβ(1–42)), phosphorylated tau (181P) (p-tau), and total tau (t-tau), have long been associated with the development of Parkinson disease (PD) and other neurodegenerative diseases. In this investi...

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Autores principales: Gao, Rui, Zhang, Guangjian, Chen, Xueqi, Yang, Aimin, Smith, Gwenn, Wong, Dean F., Zhou, Yun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072678/
https://www.ncbi.nlm.nih.gov/pubmed/27764160
http://dx.doi.org/10.1371/journal.pone.0164762
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author Gao, Rui
Zhang, Guangjian
Chen, Xueqi
Yang, Aimin
Smith, Gwenn
Wong, Dean F.
Zhou, Yun
author_facet Gao, Rui
Zhang, Guangjian
Chen, Xueqi
Yang, Aimin
Smith, Gwenn
Wong, Dean F.
Zhou, Yun
author_sort Gao, Rui
collection PubMed
description OBJECTIVE: Cerebrospinal fluid (CSF) biomarkers, such as α-synuclein (α-syn), amyloid beta peptide 1–42 (Aβ(1–42)), phosphorylated tau (181P) (p-tau), and total tau (t-tau), have long been associated with the development of Parkinson disease (PD) and other neurodegenerative diseases. In this investigation, we reported the assessment of CSF biomarkers and their correlations with vesicular monoamine transporter 2 (VMAT2) bindings measured with (18)F-9-fluoropropyl-(+)-dihydrotetrabenazine ((18)F-AV133) that is being developed as a biomarker for PD. We test the hypothesis that monoaminergic degeneration was correlated with CSF biomarker levels in untreated PD patients. METHODS: The available online data from the Parkinson’s Progression Markers Initiative study (PPMI) project were collected and analyzed, which include demographic information, clinical evaluations, CSF biomarkers (α-syn, Aβ(1–42), p-tau, and t-tau), (18)F-AV133 brain PET, and T1 weighted MRIs. Region of interest (ROI) and voxel-wise Pearson correlation between standardized uptake value ratio (SUVR) and CSF biomarkers were calculated. RESULTS: Our major findings are: 1) Compared with controls, CSF α-syn and tau levels decreased significantly in PD; 2) α-syn was closely correlated with Aβ(1–42) and tau in PD, especially in early-onset patients; and 3) hypothesis-driven ROI analysis found a significant negative correlation between CSF Aβ(1–42) levels and VMAT2 densities in post cingulate, left caudate, left anterior putamen, and left ventral striatum in PDs. CSF t-tau and p-tau levels were significantly negatively related to VMAT2 SUVRs in substantia nigra and left ventral striatum, respectively. Voxel-wise analysis showed that left caudate, parahippocampal gyrus, insula and temporal lobe were negatively correlated with Aβ(1–42). In addition, superior frontal gyrus and transverse temporal gyrus were negatively correlated with CSF p-tau levels. CONCLUSION: These results suggest that monoaminergic degeneration in PD is correlated with CSF biomarkers associated with cognitive impairment in neurodegenerative diseases including Alzheimer’s disease. The association between loss of dopamine synaptic function and pathologic protein accumulations in PD indicates an important role of CSF biomarkers in PD development.
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spelling pubmed-50726782016-10-27 CSF Biomarkers and Its Associations with (18)F-AV133 Cerebral VMAT2 Binding in Parkinson’s Disease—A Preliminary Report Gao, Rui Zhang, Guangjian Chen, Xueqi Yang, Aimin Smith, Gwenn Wong, Dean F. Zhou, Yun PLoS One Research Article OBJECTIVE: Cerebrospinal fluid (CSF) biomarkers, such as α-synuclein (α-syn), amyloid beta peptide 1–42 (Aβ(1–42)), phosphorylated tau (181P) (p-tau), and total tau (t-tau), have long been associated with the development of Parkinson disease (PD) and other neurodegenerative diseases. In this investigation, we reported the assessment of CSF biomarkers and their correlations with vesicular monoamine transporter 2 (VMAT2) bindings measured with (18)F-9-fluoropropyl-(+)-dihydrotetrabenazine ((18)F-AV133) that is being developed as a biomarker for PD. We test the hypothesis that monoaminergic degeneration was correlated with CSF biomarker levels in untreated PD patients. METHODS: The available online data from the Parkinson’s Progression Markers Initiative study (PPMI) project were collected and analyzed, which include demographic information, clinical evaluations, CSF biomarkers (α-syn, Aβ(1–42), p-tau, and t-tau), (18)F-AV133 brain PET, and T1 weighted MRIs. Region of interest (ROI) and voxel-wise Pearson correlation between standardized uptake value ratio (SUVR) and CSF biomarkers were calculated. RESULTS: Our major findings are: 1) Compared with controls, CSF α-syn and tau levels decreased significantly in PD; 2) α-syn was closely correlated with Aβ(1–42) and tau in PD, especially in early-onset patients; and 3) hypothesis-driven ROI analysis found a significant negative correlation between CSF Aβ(1–42) levels and VMAT2 densities in post cingulate, left caudate, left anterior putamen, and left ventral striatum in PDs. CSF t-tau and p-tau levels were significantly negatively related to VMAT2 SUVRs in substantia nigra and left ventral striatum, respectively. Voxel-wise analysis showed that left caudate, parahippocampal gyrus, insula and temporal lobe were negatively correlated with Aβ(1–42). In addition, superior frontal gyrus and transverse temporal gyrus were negatively correlated with CSF p-tau levels. CONCLUSION: These results suggest that monoaminergic degeneration in PD is correlated with CSF biomarkers associated with cognitive impairment in neurodegenerative diseases including Alzheimer’s disease. The association between loss of dopamine synaptic function and pathologic protein accumulations in PD indicates an important role of CSF biomarkers in PD development. Public Library of Science 2016-10-20 /pmc/articles/PMC5072678/ /pubmed/27764160 http://dx.doi.org/10.1371/journal.pone.0164762 Text en © 2016 Gao et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Gao, Rui
Zhang, Guangjian
Chen, Xueqi
Yang, Aimin
Smith, Gwenn
Wong, Dean F.
Zhou, Yun
CSF Biomarkers and Its Associations with (18)F-AV133 Cerebral VMAT2 Binding in Parkinson’s Disease—A Preliminary Report
title CSF Biomarkers and Its Associations with (18)F-AV133 Cerebral VMAT2 Binding in Parkinson’s Disease—A Preliminary Report
title_full CSF Biomarkers and Its Associations with (18)F-AV133 Cerebral VMAT2 Binding in Parkinson’s Disease—A Preliminary Report
title_fullStr CSF Biomarkers and Its Associations with (18)F-AV133 Cerebral VMAT2 Binding in Parkinson’s Disease—A Preliminary Report
title_full_unstemmed CSF Biomarkers and Its Associations with (18)F-AV133 Cerebral VMAT2 Binding in Parkinson’s Disease—A Preliminary Report
title_short CSF Biomarkers and Its Associations with (18)F-AV133 Cerebral VMAT2 Binding in Parkinson’s Disease—A Preliminary Report
title_sort csf biomarkers and its associations with (18)f-av133 cerebral vmat2 binding in parkinson’s disease—a preliminary report
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072678/
https://www.ncbi.nlm.nih.gov/pubmed/27764160
http://dx.doi.org/10.1371/journal.pone.0164762
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