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The Parkinson's progression markers initiative (PPMI) – establishing a PD biomarker cohort
Author(s) -
Marek Kenneth,
Chowdhury Sohini,
Siderowf Andrew,
Lasch Shirley,
Coffey Christopher S.,
CaspellGarcia Chelsea,
Simuni Tanya,
Jennings Danna,
Tanner Caroline M.,
Trojanowski John Q.,
Shaw Leslie M.,
Seibyl John,
Schuff Norbert,
Singleton Andrew,
Kieburtz Karl,
Toga Arthur W.,
Mollenhauer Brit,
Galasko Doug,
Chahine Lana M.,
Weintraub Daniel,
Foroud Tatiana,
TosunTurgut Duygu,
Poston Kathleen,
Arnedo Vanessa,
Frasier Mark,
Sherer Todd
Publication year - 2018
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.644
Subject(s) - medicine , biomarker , parkinson's disease , cohort , oncology , dopamine transporter , putamen , imaging biomarker , dopaminergic , disease , gastroenterology , pathology , dopamine , magnetic resonance imaging , radiology , biochemistry , chemistry
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.

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