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The Parkinson's progression markers initiative (PPMI) - establishing a PD biomarker cohort

Title: The Parkinson's progression markers initiative (PPMI) - establishing a PD biomarker cohort
Authors: Marek, K
Chowdhury, S
Siderowf, A
Lasch, S
Coffey, CS
Caspell-Garcia, C
Simuni, T
Jennings, D
Tanner, CM
Trojanowski, JQ
Shaw, LM
Seibyl, J
Schuff, N
Singleton, A
Kieburtz, K
Toga, AW
Mollenhauer, B
Galasko, D
Chahine, LM
Weintraub, D
Foroud, T
Tosun-Turgut, D
Poston, K
Arnedo, V
Frasier, M
Sherer, T
Item Type: Journal Article
Abstract: Objective The Parkinson's Progression Markers Initiative (PPMI) is an observational, international study designed to establish biomarker-defined cohorts and identify clinical, imaging, genetic, and biospecimen Parkinson's disease (PD) progression markers to accelerate disease-modifying therapeutic trials. Methods A total of 423 untreated PD, 196 Healthy Control (HC) and 64 SWEDD (scans without evidence of dopaminergic deficit) subjects were enrolled at 24 sites. To enroll PD subjects as early as possible following diagnosis, subjects were eligible with only asymmetric bradykinesia or tremor plus a dopamine transporter (DAT) binding deficit on SPECT imaging. Acquisition of data was standardized as detailed at www.ppmi-info.org. Results Approximately 9% of enrolled subjects had a single PD sign at baseline. DAT imaging excluded 16% of potential PD subjects with SWEDD. The total MDS-UPDRS for PD was 32.4 compared to 4.6 for HC and 28.2 for SWEDD. On average, PD subjects demonstrated 45% and 68% reduction in mean striatal and contralateral putamen Specific Binding Ratios (SBR), respectively. Cerebrospinal fluid (CSF) was acquired from >97% of all subjects. CSF (PD/HC/SWEDD pg/mL) α-synuclein (1845/2204/2141) was reduced in PD vs HC or SWEDD (P < 0.03). Similarly, t-tau (45/53) and p-tau (16/18) were reduced in PD versus HC (P < 0.01), Interpretation PPMI has detailed the biomarker signature for an early PD cohort defined by clinical features and imaging biomarkers. This strategy provides the framework to establish biomarker cohorts and to define longitudinal progression biomarkers to support future PD treatment trials.
Issue Date: 1-Dec-2018
Date of Acceptance: 3-Aug-2018
URI: http://hdl.handle.net/10044/1/91091
DOI: 10.1002/acn3.644
ISSN: 2328-9503
Publisher: Wiley Open Access
Start Page: 1460
End Page: 1477
Journal / Book Title: Annals of Clinical and Translational Neurology
Volume: 5
Issue: 12
Copyright Statement: © 2018 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of Am erican Neurological Association.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use anddistribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Keywords: Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences
Neurosciences & Neurology
SOCIETY-SPONSORED REVISION
CEREBROSPINAL-FLUID
ALPHA-SYNUCLEIN
RATING-SCALE
DE-NOVO
NEUROPSYCHIATRIC SYMPTOMS
COGNITIVE PERFORMANCE
AMYLOID-BETA
DISEASE
TAU
Parkinson's Progression Markers Initiative
Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences
Neurosciences & Neurology
SOCIETY-SPONSORED REVISION
CEREBROSPINAL-FLUID
ALPHA-SYNUCLEIN
RATING-SCALE
DE-NOVO
NEUROPSYCHIATRIC SYMPTOMS
COGNITIVE PERFORMANCE
AMYLOID-BETA
DISEASE
TAU
1103 Clinical Sciences
1109 Neurosciences
Publication Status: Published
Online Publication Date: 2018-10-31
Appears in Collections:Faculty of Medicine
Department of Brain Sciences



This item is licensed under a Creative Commons License Creative Commons