Journal article
CSF biomarkers associated with disease heterogeneity in early Parkinson's disease: the Parkinson's Progression Markers Initiative study
Acta neuropathologica, Vol.131(6), pp.935-949
06/2016
DOI: 10.1007/s00401-016-1552-2
PMCID: PMC5031365
PMID: 27021906
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 (α-syn), amyloid-beta1-42 (Aβ1-42), 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 α-syn, t-tau and p-tau levels, but not Aβ1-42, 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 α-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 Aβ1-42, or highest t-tau/Aβ1-42 and t-tau/α-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 α-syn was significantly associated with worse cognitive test performance. APOE ε4 genotype was associated with lower levels of Aβ1-42, 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.
Details
- Title: Subtitle
- CSF biomarkers associated with disease heterogeneity in early Parkinson's disease: the Parkinson's Progression Markers Initiative study
- Creators
- Ju-Hee Kang - Department of Pharmacology, Hypoxia-related Disease Research Center, Inha University School of Medicine, Incheon, Republic of KoreaBrit Mollenhauer - Department of Neuropathology and Neurosurgery, University Medical Center Goettingen, Göttingen, GermanyChristopher S Coffey - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USAJon B Toledo - Center for Neurodegenerative Disease Research, Institute on Aging, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USADaniel Weintraub - Department of Veterans Affairs, Philadelphia, PA, USADouglas R Galasko - Department of Neurosciences, University of California, San Diego, CA, USADavid J Irwin - Department of Neurology, Morris K. Udall Center of Excellence for Parkinson's Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USAVivianna Van Deerlin - Center for Neurodegenerative Disease Research, Institute on Aging, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USAAlice S Chen-Plotkin - Department of Neurology, Morris K. Udall Center of Excellence for Parkinson's Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USAChelsea Caspell-Garcia - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USATeresa Waligórska - Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, 7.103 Founders Pavilion 3400 Spruce Street, Philadelphia, PA, 19104, USAPeggy Taylor - BioLegend Inc., Dedham, MA, USANirali Shah - Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, 7.103 Founders Pavilion 3400 Spruce Street, Philadelphia, PA, 19104, USASarah Pan - Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, 7.103 Founders Pavilion 3400 Spruce Street, Philadelphia, PA, 19104, USAPawel Zero - Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, 7.103 Founders Pavilion 3400 Spruce Street, Philadelphia, PA, 19104, USAMark Frasier - The Michael J. Fox Foundation for Parkinson's Research, New York, NY, USAKenneth Marek - Institute for Neurodegenerative Disorders, New Haven, CT, USAKarl Kieburtz - Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USADanna Jennings - Institute for Neurodegenerative Disorders, New Haven, CT, USACaroline M Tanner - University of California-San Francisco and San Francisco Veteran's Affairs Medical Center, San Francisco, CA, USATanya Simuni - Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USAAndrew Singleton - Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USAArthur W Toga - Laboratory of Neuro Imaging, The Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USASohini Chowdhury - The Michael J. Fox Foundation for Parkinson's Research, New York, NY, USAJohn Q Trojanowski - Department of Neurology, Morris K. Udall Center of Excellence for Parkinson's Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USALeslie M Shaw - Center for Neurodegenerative Disease Research, Institute on Aging, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Les.Shaw@uphs.upenn.eduParkinson’s Progression Marker Initiative
- Resource Type
- Journal article
- Publication Details
- Acta neuropathologica, Vol.131(6), pp.935-949
- DOI
- 10.1007/s00401-016-1552-2
- PMID
- 27021906
- PMCID
- PMC5031365
- NLM abbreviation
- Acta Neuropathol
- ISSN
- 0001-6322
- eISSN
- 1432-0533
- Publisher
- Germany
- Grant note
- Z01 AG000949 / Intramural NIH HHS K23 NS088341 / NINDS NIH HHS P50 NS053488 / NINDS NIH HHS T32 AG000255 / NIA NIH HHS U01 NS082134 / NINDS NIH HHS
- Language
- English
- Date published
- 06/2016
- Academic Unit
- Biostatistics
- Record Identifier
- 9983997444402771
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