Longitudinal CSF biomarkers in patients with early Parkinson disease and healthy controls

Brit Mollenhauer; Chelsea J Caspell-Garcia; Christopher S Coffey; Peggy Taylor; Leslie M Shaw; John Q Trojanowski; Andy Singleton; Mark Frasier; Kenneth Marek; Douglas Galasko; Parkinson's Progression Marker Initiative

doi:10.1212/WNL.0000000000004609

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Longitudinal CSF biomarkers in patients with early Parkinson disease and healthy controls

Journal article

Open access

Peer reviewed

Longitudinal CSF biomarkers in patients with early Parkinson disease and healthy controls

Brit Mollenhauer, Chelsea J Caspell-Garcia, Christopher S Coffey, Peggy Taylor, Leslie M Shaw, John Q Trojanowski, Andy Singleton, Mark Frasier, Kenneth Marek, Douglas Galasko, …

Neurology, Vol.89(19), pp.1959-1969

11/07/2017

DOI: 10.1212/WNL.0000000000004609

PMCID: PMC5679418

PMID: 29030452

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Abstract

To analyze longitudinal levels of CSF biomarkers in drug-naive patients with Parkinson disease (PD) and healthy controls (HC), examine the extent to which these biomarker changes relate to clinical measures of PD, and identify what may influence them. CSF α-synuclein (α-syn), total and phosphorylated tau (t- and p-tau), and β-amyloid 1-42 (Aβ42) were measured at baseline and 6 and 12 months in 173 patients with PD and 112 matched HC in the international multicenter Parkinson's Progression Marker Initiative. Baseline clinical and demographic variables, PD medications, neuroimaging, and genetic variables were evaluated as potential predictors of CSF biomarker changes. CSF biomarkers were stable over 6 and 12 months, and there was a small but significant increase in CSF Aβ42 in both patients with patients with PD and HC from baseline to 12 months. The t-tau remained stable. The p-tau increased marginally more in patients with PD than in HC. α-syn remained relatively stable in patients with PD and HC. Ratios of p-tau/t-tau increased, while t-tau/Aβ42 decreased over 12 months in patients with PD. CSF biomarker changes did not correlate with changes in Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale motor scores or dopamine imaging. CSF α-syn levels at 12 months were lower in patients with PD treated with dopamine replacement therapy, especially dopamine agonists. These core CSF biomarkers remained stable over 6 and 12 months in patients with early PD and HC. PD medication use may influence CSF α-syn. Novel biomarkers are needed to better profile progressive neurodegeneration in PD.

Severity of Illness Index

Parkinson Disease - diagnostic imaging

Peptide Fragments - cerebrospinal fluid

Humans

Middle Aged

Tomography, Emission-Computed, Single-Photon

Male

tau Proteins - cerebrospinal fluid

Parkinson Disease - genetics

Case-Control Studies

Time Factors

Apolipoproteins E - genetics

Parkinson Disease - cerebrospinal fluid

Amyloid beta-Peptides - cerebrospinal fluid

Polymorphism, Single Nucleotide - genetics

Female

Aged

Retrospective Studies

Longitudinal Studies

Dopamine - metabolism

Details

Title: Subtitle: Longitudinal CSF biomarkers in patients with early Parkinson disease and healthy controls
Creators: Brit Mollenhauer - From the Department of Neurology (B.M.), University Medical Center, Göttingen; Paracelsus-Elena-Klinik (B.M.), Kassel, Germany; Department of Biostatistics (C.J.C.-G., C.S.C.), College of Public Health, University of Iowa, Iowa City; BioLegend Inc. (P.T.), San Diego, CA; Department of Pathology & Laboratory Medicine (L.M.S., J.Q.T.), Center for Neurodegenerative Disease Research, Institute on Aging (L.M.S. , J.Q.T.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Molecular Genetics Section (A.S.), Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD; The Michael J. Fox Foundation for Parkinson's Research (M.F.), New York, NY; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; and Department of Neurosciences (D.G.), University of California, San Diego. brit.mollenhauer@med.uni-goettingen.de
Chelsea J Caspell-Garcia - From the Department of Neurology (B.M.), University Medical Center, Göttingen; Paracelsus-Elena-Klinik (B.M.), Kassel, Germany; Department of Biostatistics (C.J.C.-G., C.S.C.), College of Public Health, University of Iowa, Iowa City; BioLegend Inc. (P.T.), San Diego, CA; Department of Pathology & Laboratory Medicine (L.M.S., J.Q.T.), Center for Neurodegenerative Disease Research, Institute on Aging (L.M.S. , J.Q.T.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Molecular Genetics Section (A.S.), Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD; The Michael J. Fox Foundation for Parkinson's Research (M.F.), New York, NY; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; and Department of Neurosciences (D.G.), University of California, San Diego
Christopher S Coffey - From the Department of Neurology (B.M.), University Medical Center, Göttingen; Paracelsus-Elena-Klinik (B.M.), Kassel, Germany; Department of Biostatistics (C.J.C.-G., C.S.C.), College of Public Health, University of Iowa, Iowa City; BioLegend Inc. (P.T.), San Diego, CA; Department of Pathology & Laboratory Medicine (L.M.S., J.Q.T.), Center for Neurodegenerative Disease Research, Institute on Aging (L.M.S. , J.Q.T.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Molecular Genetics Section (A.S.), Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD; The Michael J. Fox Foundation for Parkinson's Research (M.F.), New York, NY; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; and Department of Neurosciences (D.G.), University of California, San Diego
Peggy Taylor - From the Department of Neurology (B.M.), University Medical Center, Göttingen; Paracelsus-Elena-Klinik (B.M.), Kassel, Germany; Department of Biostatistics (C.J.C.-G., C.S.C.), College of Public Health, University of Iowa, Iowa City; BioLegend Inc. (P.T.), San Diego, CA; Department of Pathology & Laboratory Medicine (L.M.S., J.Q.T.), Center for Neurodegenerative Disease Research, Institute on Aging (L.M.S. , J.Q.T.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Molecular Genetics Section (A.S.), Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD; The Michael J. Fox Foundation for Parkinson's Research (M.F.), New York, NY; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; and Department of Neurosciences (D.G.), University of California, San Diego
Leslie M Shaw - From the Department of Neurology (B.M.), University Medical Center, Göttingen; Paracelsus-Elena-Klinik (B.M.), Kassel, Germany; Department of Biostatistics (C.J.C.-G., C.S.C.), College of Public Health, University of Iowa, Iowa City; BioLegend Inc. (P.T.), San Diego, CA; Department of Pathology & Laboratory Medicine (L.M.S., J.Q.T.), Center for Neurodegenerative Disease Research, Institute on Aging (L.M.S. , J.Q.T.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Molecular Genetics Section (A.S.), Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD; The Michael J. Fox Foundation for Parkinson's Research (M.F.), New York, NY; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; and Department of Neurosciences (D.G.), University of California, San Diego
John Q Trojanowski - From the Department of Neurology (B.M.), University Medical Center, Göttingen; Paracelsus-Elena-Klinik (B.M.), Kassel, Germany; Department of Biostatistics (C.J.C.-G., C.S.C.), College of Public Health, University of Iowa, Iowa City; BioLegend Inc. (P.T.), San Diego, CA; Department of Pathology & Laboratory Medicine (L.M.S., J.Q.T.), Center for Neurodegenerative Disease Research, Institute on Aging (L.M.S. , J.Q.T.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Molecular Genetics Section (A.S.), Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD; The Michael J. Fox Foundation for Parkinson's Research (M.F.), New York, NY; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; and Department of Neurosciences (D.G.), University of California, San Diego
Andy Singleton - From the Department of Neurology (B.M.), University Medical Center, Göttingen; Paracelsus-Elena-Klinik (B.M.), Kassel, Germany; Department of Biostatistics (C.J.C.-G., C.S.C.), College of Public Health, University of Iowa, Iowa City; BioLegend Inc. (P.T.), San Diego, CA; Department of Pathology & Laboratory Medicine (L.M.S., J.Q.T.), Center for Neurodegenerative Disease Research, Institute on Aging (L.M.S. , J.Q.T.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Molecular Genetics Section (A.S.), Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD; The Michael J. Fox Foundation for Parkinson's Research (M.F.), New York, NY; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; and Department of Neurosciences (D.G.), University of California, San Diego
Mark Frasier - From the Department of Neurology (B.M.), University Medical Center, Göttingen; Paracelsus-Elena-Klinik (B.M.), Kassel, Germany; Department of Biostatistics (C.J.C.-G., C.S.C.), College of Public Health, University of Iowa, Iowa City; BioLegend Inc. (P.T.), San Diego, CA; Department of Pathology & Laboratory Medicine (L.M.S., J.Q.T.), Center for Neurodegenerative Disease Research, Institute on Aging (L.M.S. , J.Q.T.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Molecular Genetics Section (A.S.), Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD; The Michael J. Fox Foundation for Parkinson's Research (M.F.), New York, NY; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; and Department of Neurosciences (D.G.), University of California, San Diego
Kenneth Marek - From the Department of Neurology (B.M.), University Medical Center, Göttingen; Paracelsus-Elena-Klinik (B.M.), Kassel, Germany; Department of Biostatistics (C.J.C.-G., C.S.C.), College of Public Health, University of Iowa, Iowa City; BioLegend Inc. (P.T.), San Diego, CA; Department of Pathology & Laboratory Medicine (L.M.S., J.Q.T.), Center for Neurodegenerative Disease Research, Institute on Aging (L.M.S. , J.Q.T.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Molecular Genetics Section (A.S.), Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD; The Michael J. Fox Foundation for Parkinson's Research (M.F.), New York, NY; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; and Department of Neurosciences (D.G.), University of California, San Diego
Douglas Galasko - From the Department of Neurology (B.M.), University Medical Center, Göttingen; Paracelsus-Elena-Klinik (B.M.), Kassel, Germany; Department of Biostatistics (C.J.C.-G., C.S.C.), College of Public Health, University of Iowa, Iowa City; BioLegend Inc. (P.T.), San Diego, CA; Department of Pathology & Laboratory Medicine (L.M.S., J.Q.T.), Center for Neurodegenerative Disease Research, Institute on Aging (L.M.S. , J.Q.T.), and Morris K. Udall Center of Excellence for Parkinson's Disease Research (J.Q.T.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Molecular Genetics Section (A.S.), Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD; The Michael J. Fox Foundation for Parkinson's Research (M.F.), New York, NY; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; and Department of Neurosciences (D.G.), University of California, San Diego
Parkinson's Progression Marker Initiative
Resource Type: Journal article
Publication Details: Neurology, Vol.89(19), pp.1959-1969
DOI: 10.1212/WNL.0000000000004609
PMID: 29030452
PMCID: PMC5679418
NLM abbreviation: Neurology
ISSN: 0028-3878
eISSN: 1526-632X
Publisher: United States
Grant note: P41 EB015922 / NIBIB NIH HHS P50 AG005131 / NIA NIH HHS P30 AG010124 / NIA NIH HHS
Language: English
Date published: 11/07/2017
Academic Unit: Biostatistics
Record Identifier: 9983997445702771

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