Dataset Information

CSF biomarkers associated with disease heterogeneity in early Parkinson's disease: the Parkinson's Progression Markers Initiative study.

ABSTRACT: The development of biomarkers to predict the progression of Parkinson's disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson's Progression Markers Initiative (PPMI) study is an ongoing international multicenter, prospective study to validate biomarkers in drug-naïve PD patients and matched healthy controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (?-syn), amyloid-beta1-42 (A?1-42), total tau (t-tau), and tau phosphorylated at Thr181 (p-tau) in 660 PPMI subjects at baseline, and correlated these data with measures of the clinical features of these subjects. We found that CSF ?-syn, t-tau and p-tau levels, but not A?1-42, were significantly lower in PD compared with HC, while the diagnostic value of the individual CSF biomarkers for PD diagnosis was limited due to large overlap. The level of ?-syn, but not other biomarkers, was significantly lower in PD patients with non-tremor-dominant phenotype compared with tremor-dominant phenotype. In addition, in PD patients the lowest A?1-42, or highest t-tau/A?1-42 and t-tau/?-syn quintile in PD patients were associated with more severe non-motor dysfunction compared with the highest or lowest quintiles, respectively. In a multivariate regression model, lower ?-syn was significantly associated with worse cognitive test performance. APOE ?4 genotype was associated with lower levels of A?1-42, but neither with PD diagnosis nor cognition. Our data suggest that the measurement of CSF biomarkers in early-stage PD patients may relate to disease heterogeneity seen in PD. Longitudinal observations in PPMI subjects are needed to define their prognostic performance.

SUBMITTER: Kang JH

PROVIDER: S-EPMC5031365 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CSF biomarkers associated with disease heterogeneity in early Parkinson's disease: the Parkinson's Progression Markers Initiative study.

Kang Ju-Hee JH Mollenhauer Brit B Coffey Christopher S CS Toledo Jon B JB Weintraub Daniel D Galasko Douglas R DR Irwin David J DJ Van Deerlin Vivianna V Chen-Plotkin Alice S AS Caspell-Garcia Chelsea C Waligórska Teresa T Taylor Peggy P Shah Nirali N Pan Sarah S Zero Pawel P Frasier Mark M Marek Kenneth K Kieburtz Karl K Jennings Danna D Tanner Caroline M CM Simuni Tanya T Singleton Andrew A Toga Arthur W AW Chowdhury Sohini S Trojanowski John Q JQ Shaw Leslie M LM

Acta neuropathologica 20160328 6

The development of biomarkers to predict the progression of Parkinson's disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson's Progression Markers Initiative (PPMI) study is an ongoing international multicenter, prospective study to validate biomarkers in drug-naïve PD patients and matched healthy controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (α-syn), amyloid-beta1-42 (Aβ1-42), total tau ...[more]

PMID: 27021906

Similar Datasets

Project description:BackgroundIdentifying a meaningful progression metric for Parkinson's disease (PD) that reflects heterogeneity remains a challenge.ObjectiveTo assess the frequency and baseline predictors of progression to clinically relevant motor and non-motor PD milestones.MethodsUsing data from the Parkinson's Progression Markers Initiative (PPMI) de novo PD cohort, we monitored 25 milestones across six domains ("walking and balance"; "motor complications"; "cognition"; "autonomic dysfunction"; "functional dependence"; "activities of daily living"). Milestones were intended to be severe enough to reflect meaningful disability. We assessed the proportion of participants reaching any milestone; evaluated which occurred most frequently; and conducted a time-to-first-event analysis exploring whether baseline characteristics were associated with progression.ResultsHalf of participants reached at least one milestone within five years. Milestones within the cognitive, functional dependence, and autonomic dysfunction domains were reached most often. Among participants who reached a milestone at an annual follow-up visit and remained active in the study, 82% continued to meet criteria for any milestone at one or more subsequent annual visits and 55% did so at the next annual visit. In multivariable analysis, baseline features predicting faster time to reaching a milestone included age (p < 0.0001), greater MDS-UPDRS total scores (p < 0.0001), higher GDS-15 depression scores (p = 0.0341), lower dopamine transporter binding (p = 0.0043), and lower CSF total α-synuclein levels (p = 0.0030). Symptomatic treatment was not significantly associated with reaching a milestone (p = 0.1639).ConclusionClinically relevant milestones occur frequently, even in early PD. Milestones were significantly associated with baseline clinical and biological markers, but not with symptomatic treatment. Further studies are necessary to validate these results, further assess the stability of milestones, and explore translating them into an outcome measure suitable for observational and therapeutic studies.

Project description:Background: Orthostatic hypotension (OH) in Parkinson's disease (PD) can lead to falls, impair quality of life, and increase mortality. A trajectory analysis of OH could be useful to predict and prevent the hypotension incidence early. Methods: The longitudinal data of 660 patients with PD with disease duration up to 12 years were extracted from an integrated PD database. We used latent class mixed modeling (LCMM) to identify patient subgroups, demonstrating trajectories of changes in orthostatic blood pressure (BP) over time. The optimal number of subgroups was selected by several criteria including the Bayesian Information Criterion. Baseline information comparison between groups and backward stepwise logistic regression were conducted to define the distinguishing characteristics of these subgroups and to investigate the predictors for BP trajectory. Results: We identified three trajectories for each orthostatic change of systolic blood pressure (ΔSBP), namely, Class 1 (i.e., the increasing class) consisted of 18 participants with low ΔSBP that increased continuously during the follow-up; Class 2 (i.e., the low-stable class) consisted of 610 participants with low ΔSBP that remained low throughout the follow-up; and Class 3 (i.e., the high-stable class) consisted of 32 participants with high ΔSBP at baseline that was relatively stable throughout the follow-up. Several parameters differed among subgroups, but only male sex [odds ratio (OR) = 4.687, 95% confidence interval (CI) = 1.024-21.459], lower supine diastolic blood pressure (DBP) (OR = 0.934, 95% CI = 0.876-0.996), and lower level of total protein at baseline (OR = 0.812, 95% CI = 0.700-0.941) were significant predictors of an increasing ΔSBP trajectory. Conclusion: This study provides new information on the longitudinal development of ΔSBP in patients with PD with distinct trajectories of rapidly increasing, low-stable, and high-stable class. The parameters such as male sex, lower supine DBP, and lower total proteins help to identify the rapidly increasing class.

Dataset Information

CSF biomarkers associated with disease heterogeneity in early Parkinson's disease: the Parkinson's Progression Markers Initiative study.

Publications

CSF biomarkers associated with disease heterogeneity in early Parkinson's disease: the Parkinson's Progression Markers Initiative study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets