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CSF Biomarkers and Its Associations with 18F-AV133 Cerebral VMAT2 Binding in Parkinson's Disease-A Preliminary Report.
PLoS One. 2016; 11(10):e0164762.Plos

Abstract

OBJECTIVE

Cerebrospinal fluid (CSF) biomarkers, such as α-synuclein (α-syn), amyloid beta peptide 1-42 (Aβ1-42), 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 18F-9-fluoropropyl-(+)-dihydrotetrabenazine (18F-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, Aβ1-42, p-tau, and t-tau), 18F-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 Aβ1-42 and tau in PD, especially in early-onset patients; and 3) hypothesis-driven ROI analysis found a significant negative correlation between CSF Aβ1-42 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 Aβ1-42. 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.

Authors+Show Affiliations

Department of Nuclear Medicine, the First Affiliated Hospital of Xian Jiaotong University, Xi'an, Shaanxi 710061, China. The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, United States of America.Department of Surgery, the First Affiliated Hospital of Xian Jiaotong University, Xi'an, Shaanxi 710061, China.The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, United States of America. Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China.Department of Nuclear Medicine, the First Affiliated Hospital of Xian Jiaotong University, Xi'an, Shaanxi 710061, China.Division of Geriatric Psychiatry and Neuropsychiatry, Johns Hopkins Bayview Medical Center, Baltimore, Maryland 21287, United States of America.The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, United States of America. Department of Psychiatry, Johns Hopkins University, Baltimore, Maryland 21205, United States of America. Department of Neurology, Johns Hopkins University, Baltimore, Maryland 21205, United States of America. Department of Neuroscience, Johns Hopkins University, Baltimore, Maryland 21205, United States of America.The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, United States of America.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27764160

Citation

Gao, Rui, et al. "CSF Biomarkers and Its Associations With 18F-AV133 Cerebral VMAT2 Binding in Parkinson's Disease-A Preliminary Report." PloS One, vol. 11, no. 10, 2016, pp. e0164762.
Gao R, Zhang G, Chen X, et al. CSF Biomarkers and Its Associations with 18F-AV133 Cerebral VMAT2 Binding in Parkinson's Disease-A Preliminary Report. PLoS One. 2016;11(10):e0164762.
Gao, R., Zhang, G., Chen, X., Yang, A., Smith, G., Wong, D. F., & Zhou, Y. (2016). CSF Biomarkers and Its Associations with 18F-AV133 Cerebral VMAT2 Binding in Parkinson's Disease-A Preliminary Report. PloS One, 11(10), e0164762. https://doi.org/10.1371/journal.pone.0164762
Gao R, et al. CSF Biomarkers and Its Associations With 18F-AV133 Cerebral VMAT2 Binding in Parkinson's Disease-A Preliminary Report. PLoS One. 2016;11(10):e0164762. PubMed PMID: 27764160.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CSF Biomarkers and Its Associations with 18F-AV133 Cerebral VMAT2 Binding in Parkinson's Disease-A Preliminary Report. AU - Gao,Rui, AU - Zhang,Guangjian, AU - Chen,Xueqi, AU - Yang,Aimin, AU - Smith,Gwenn, AU - Wong,Dean F, AU - Zhou,Yun, Y1 - 2016/10/20/ PY - 2016/05/04/received PY - 2016/09/30/accepted PY - 2016/10/21/pubmed PY - 2017/6/6/medline PY - 2016/10/21/entrez SP - e0164762 EP - e0164762 JF - PloS one JO - PLoS One VL - 11 IS - 10 N2 - OBJECTIVE: Cerebrospinal fluid (CSF) biomarkers, such as α-synuclein (α-syn), amyloid beta peptide 1-42 (Aβ1-42), 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 18F-9-fluoropropyl-(+)-dihydrotetrabenazine (18F-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, Aβ1-42, p-tau, and t-tau), 18F-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 Aβ1-42 and tau in PD, especially in early-onset patients; and 3) hypothesis-driven ROI analysis found a significant negative correlation between CSF Aβ1-42 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 Aβ1-42. 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/27764160/CSF_Biomarkers_and_Its_Associations_with_18F_AV133_Cerebral_VMAT2_Binding_in_Parkinson's_Disease_A_Preliminary_Report_ L2 - https://dx.plos.org/10.1371/journal.pone.0164762 DB - PRIME DP - Unbound Medicine ER -