{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kang JH"],"funding":["Intramural NIH HHS","NIA NIH HHS","NIMH NIH HHS","NINDS NIH HHS"],"pagination":["1277-87"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4034348"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["70(10)"],"pubmed_abstract":["IMPORTANCE:We observed a significant correlation between cerebrospinal fluid (CSF) levels of tau proteins and ?-synuclein, but not ?-amyloid 1-42 (A?1-42), and lower concentration of CSF biomarkers, as compared with healthy controls, in a cohort of entirely untreated patients with Parkinson disease (PD) at the earliest stage of the disease studied so far. OBJECTIVE:To evaluate the baseline characteristics and relationship to clinical features of CSF biomarkers (A?1-42, total tau [T-tau], tau phosphorylated at threonine 181 [P-tau181], and ?-synuclein) in drug-naive patients with early PD and demographically matched healthy controls enrolled in the Parkinson's Progression Markers Initiative (PPMI) study. DESIGN, SETTING, AND PARTICIPANTS:Cross-sectional study of the initial 102 research volunteers (63 patients with PD and 39 healthy controls) of the PPMI cohort. MAIN OUTCOMES AND MEASURES:The CSF biomarkers were measured by INNO-BIA AlzBio3 immunoassay (A?1-42, T-tau, and P-tau181; Innogenetics Inc) or by enzyme-linked immunosorbent assay (?-synuclein). Clinical features including diagnosis, demographic characteristics, motor, neuropsychiatric, and cognitive assessments, and DaTscan were systematically assessed according to the PPMI study protocol. RESULTS:Slightly, but significantly, lower levels of A?1-42, T-tau, P-tau181, ?-synuclein, and T-tau/A?1-42 were seen in subjects with PD compared with healthy controls but with a marked overlap between groups. Using multivariate regression analysis, we found that lower A?1-42 and P-tau181 levels were associated with PD diagnosis and that decreased CSF T-tau and ?-synuclein were associated with increased motor severity. Notably, when we classified patients with PD by their motor phenotypes, lower CSF A?1-42 and P-tau181 concentrations were associated with the postural instability-gait disturbance-dominant phenotype but not with the tremor-dominant or intermediate phenotype. Finally, we found a significant correlation of the levels of ?-synuclein with the levels of T-tau and P-tau181. CONCLUSIONS AND RELEVANCE:In this first report of CSF biomarkers in PPMI study subjects,we found that measures of CSF A?1-42, T-tau, P-tau181, and ?-synuclein have prognostic and diagnostic potential in early-stage PD. Further investigations using the entire PPMI cohort will test the predictive performance of CSF biomarkers for PD progression"],"journal":["JAMA neurology"],"pubmed_title":["Association of cerebrospinal fluid ?-amyloid 1-42, T-tau, P-tau181, and ?-synuclein levels with clinical features of drug-naive patients with early Parkinson disease."],"pmcid":["PMC4034348"],"funding_grant_id":["Z01 AG000949-03","P50NS053488-05","Z01 AG000949","U01 NS082134","U01 AG024904","Z01AG000949-06","P50 NS038377","K23 MH092735","01AG000949-06","P50 NS053488","K23MH092735","T32 AG000255"],"pubmed_authors":["Rees L","Crawford K","Jennings D","Caspell C","Flagg E","Williams K","James A","Trojanowski JQ","Poewe W","Leverenz J","Waligorska T","Coffey CS","Taylor P","Yankey J","Rowe D","Brooks D","Irwin DJ","Uribe L","Thomas CA","Richard I","Mari Z","Standaert D","Hunter C","Galasko D","Berg D","Espay A","Meunier C","Isaacson S","Chen-Plotkin AS","Kieburtz K","Singleton A","Malferrari G","Barone P","Mendick S","Frank S","Mule J","Hawkins K","Leary L","Fontaine D","Russell D","Seibyl J","Hauser R","Shill H","Siderowf A","Scutti A","Stern M","Marek K","Lasch S","Casaceli C","Sommerfeld B","Mollenhauer B","Factor S","Oertel W","Jankovic J","Gauss K","Rudolph A","Frasier M","Chowdhury S","Schuff N","McCoy A","Toga AW","Baca M","Ranola M","Sprenger F","Simuni T","Guthrie S","Sherer T","Pighetti E","Darin A","Casalin P","Pan S","Fernandez H","Espay K","Parkinson's Progression Markers Initiative","Hogarth P","Shah B","Kang JH","Willeke D","Tanner CM","Shaw LM","Deeley C"],"additional_accession":[]},"is_claimable":false,"name":"Association of cerebrospinal fluid ?-amyloid 1-42, T-tau, P-tau181, and ?-synuclein levels with clinical features of drug-naive patients with early Parkinson disease.","description":"IMPORTANCE:We observed a significant correlation between cerebrospinal fluid (CSF) levels of tau proteins and ?-synuclein, but not ?-amyloid 1-42 (A?1-42), and lower concentration of CSF biomarkers, as compared with healthy controls, in a cohort of entirely untreated patients with Parkinson disease (PD) at the earliest stage of the disease studied so far. OBJECTIVE:To evaluate the baseline characteristics and relationship to clinical features of CSF biomarkers (A?1-42, total tau [T-tau], tau phosphorylated at threonine 181 [P-tau181], and ?-synuclein) in drug-naive patients with early PD and demographically matched healthy controls enrolled in the Parkinson's Progression Markers Initiative (PPMI) study. DESIGN, SETTING, AND PARTICIPANTS:Cross-sectional study of the initial 102 research volunteers (63 patients with PD and 39 healthy controls) of the PPMI cohort. MAIN OUTCOMES AND MEASURES:The CSF biomarkers were measured by INNO-BIA AlzBio3 immunoassay (A?1-42, T-tau, and P-tau181; Innogenetics Inc) or by enzyme-linked immunosorbent assay (?-synuclein). Clinical features including diagnosis, demographic characteristics, motor, neuropsychiatric, and cognitive assessments, and DaTscan were systematically assessed according to the PPMI study protocol. RESULTS:Slightly, but significantly, lower levels of A?1-42, T-tau, P-tau181, ?-synuclein, and T-tau/A?1-42 were seen in subjects with PD compared with healthy controls but with a marked overlap between groups. Using multivariate regression analysis, we found that lower A?1-42 and P-tau181 levels were associated with PD diagnosis and that decreased CSF T-tau and ?-synuclein were associated with increased motor severity. Notably, when we classified patients with PD by their motor phenotypes, lower CSF A?1-42 and P-tau181 concentrations were associated with the postural instability-gait disturbance-dominant phenotype but not with the tremor-dominant or intermediate phenotype. Finally, we found a significant correlation of the levels of ?-synuclein with the levels of T-tau and P-tau181. CONCLUSIONS AND RELEVANCE:In this first report of CSF biomarkers in PPMI study subjects,we found that measures of CSF A?1-42, T-tau, P-tau181, and ?-synuclein have prognostic and diagnostic potential in early-stage PD. Further investigations using the entire PPMI cohort will test the predictive performance of CSF biomarkers for PD progression","dates":{"release":"2013-01-01T00:00:00Z","publication":"2013 Oct","modification":"2020-10-31T09:17:38Z","creation":"2019-03-27T01:28:52Z"},"accession":"S-EPMC4034348","cross_references":{"pubmed":["23979011"],"doi":["10.1001/jamaneurol.2013.3861"]}}