title: CSF Biomarkers and Its Associations with 18F-AV133 Cerebral VMAT2 Binding in Parkinson's Disease-A Preliminary Report.
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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Rui
authors.initials: R
authors.lastname: Gao
authors.affiliation: Department of Surgery, the First Affiliated Hospital of Xian Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Guangjian
authors.initials: G
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Xueqi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Nuclear Medicine, the First Affiliated Hospital of Xian Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Yang
authors.affiliation: Division of Geriatric Psychiatry and Neuropsychiatry, Johns Hopkins Bayview Medical Center, Baltimore, Maryland 21287, United States of America.
authors.forename: Gwenn
authors.initials: G
authors.lastname: Smith
authors.affiliation: 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.
authors.forename: Dean F
authors.initials: DF
authors.lastname: Wong
authors.affiliation: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, United States of America.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D005260:Female; D005462:Fluorine Radioisotopes / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging* / Q000378:metabolism; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D005462:Fluorine Radioisotopes; C054369:MAPT protein, human; C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins; D051844:alpha-Synuclein; D016875:tau Proteins; C549477:florbenazine F 18; D013747:Tetrabenazine