Association of Cerebrospinal Fluid β-Amyloid 1-42, T-tau, P-tau181, and α-Synuclein Levels With Clinical Features of Drug-Naive Patients With Early Parkinson Disease
Identifieur interne : 000422 ( Ncbi/Checkpoint ); précédent : 000421; suivant : 000423Association of Cerebrospinal Fluid β-Amyloid 1-42, T-tau, P-tau181, and α-Synuclein Levels With Clinical Features of Drug-Naive Patients With Early Parkinson Disease
Auteurs : Ju Kang [Corée du Sud] ; David Irwin ; Alice Chen ; Andrew Siderowf [États-Unis] ; Chelsea Caspell ; Christopher Coffey ; Teresa Walig ; Peggy Taylor [États-Unis] ; Sarah Pan ; Mark Frasier [États-Unis] ; Kenneth Marek [États-Unis] ; Karl Kieburtz [États-Unis] ; Danna Jennings [États-Unis] ; Tanya Simuni [États-Unis] ; Caroline Tanner [États-Unis] ; Andrew Singleton [États-Unis] ; Arthur Toga [États-Unis] ; Sohini Chowdhury [États-Unis] ; Brit Mollenhauer [Allemagne] ; John Trojanowski ; Leslie ShawSource :
- JAMA neurology [ 2168-6149 ] ; 2013.
English descriptors
- KwdEn :
- Amyloid beta-Peptides (cerebrospinal fluid), Case-Control Studies, Cohort Studies, Female, Humans, Male, Memory (physiology), Middle Aged, Movement (physiology), Neuropsychological Tests, Parkinson Disease (cerebrospinal fluid), Parkinson Disease (physiopathology), Peptide Fragments (cerebrospinal fluid), Phosphorylation, Regression Analysis, Severity of Illness Index, Statistics as Topic, Threonine (metabolism), Verbal Learning (physiology), alpha-Synuclein (cerebrospinal fluid), tau Proteins (cerebrospinal fluid).
- MESH :
- chemical , cerebrospinal fluid : Amyloid beta-Peptides, Peptide Fragments, alpha-Synuclein, tau Proteins.
- cerebrospinal fluid : Parkinson Disease.
- chemical , metabolism : Threonine.
- physiology : Memory, Movement, Verbal Learning.
- physiopathology : Parkinson Disease.
- Case-Control Studies, Cohort Studies, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Phosphorylation, Regression Analysis, Severity of Illness Index, Statistics as Topic.
Abstract
We observed a significant correlation between cerebrospinal fluid (CSF) levels of tau proteins and α-synuclein, but not β-amyloid 1–42 (Aβ1–42), and lower concentration of CSF biomarkers, as compared with healthy controls, in a cohort of entirely untreated patients with Parkinson disease (PD) at the earliest stage of the disease studied so far.
To evaluate the baseline characteristics and relationship to clinical features of CSF biomarkers (Aβ1–42, total tau [T-tau], tau phosphorylated at threonine 181 [P-tau181], and α-synuclein) in drug-naive patients with early PD and demographically matched healthy controls enrolled in the Parkinson’s Progression Markers Initiative (PPMI) study.
Cross-sectional study of the initial 102 research volunteers (63 patients with PD and 39 healthy controls) of the PPMI cohort.
The CSF biomarkers were measured by INNO-BIA AlzBio3 immunoassay (Aβ1–42, T-tau, and P-tau181; Innogenetics Inc) or by enzyme-linked immunosorbent assay (α-synuclein). Clinical features including diagnosis, demographic characteristics, motor, neuropsychiatric, and cognitive assessments, and DaTscan were systematically assessed according to the PPMI study protocol.
Slightly, but significantly, lower levels of Aβ1–42, T-tau, P-tau181, α-synuclein, and T-tau/Aβ1–42 were seen in subjects with PD compared with healthy controls but with a marked overlap between groups. Using multivariate regression analysis, we found that lower Aβ1–42 and P-tau181 levels were associated with PD diagnosis and that decreased CSF T-tau and α-synuclein were associated with increased motor severity. Notably, when we classified patients with PD by their motor phenotypes, lower CSF Aβ1–42 and P-tau181 concentrations were associated with the postural instability–gait disturbance–dominant phenotype but not with the tremor-dominant or intermediate phenotype. Finally, we found a significant correlation of the levels of α-synuclein with the levels of T-tau and P-tau181.
In this first report of CSF biomarkers in PPMI study subjects, we found that measures of CSF Aβ1–42, T-tau, P-tau181, and α-synuclein have prognostic and diagnostic potential in early-stage PD. Further investigations using the entire PPMI cohort will test the predictive performance of CSF biomarkers for PD progression.
Url:
DOI: 10.1001/jamaneurol.2013.3861
PubMed: 23979011
PubMed Central: 4034348
Affiliations:
- Allemagne, Corée du Sud, États-Unis
- Californie, Connecticut, District de Kassel, Hesse (Land), Illinois, Maryland, Massachusetts, Pennsylvanie, État de New York
- Cassel (Hesse), Los Angeles
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PMC:4034348Le document en format XML
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, and α-Synuclein Levels With Clinical Features of Drug-Naive Patients With Early Parkinson Disease</title>
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<author><name sortKey="Chen Plotkin, Alice S" sort="Chen Plotkin, Alice S" uniqKey="Chen Plotkin A" first="Alice" last="Chen">Alice Chen</name>
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<author><name sortKey="Coffey, Christopher S" sort="Coffey, Christopher S" uniqKey="Coffey C" first="Christopher" last="Coffey">Christopher Coffey</name>
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<author><name sortKey="Walig Rska, Teresa" sort="Walig Rska, Teresa" uniqKey="Walig Rska T" first="Teresa" last="Walig">Teresa Walig</name>
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<author><name sortKey="Taylor, Peggy" sort="Taylor, Peggy" uniqKey="Taylor P" first="Peggy" last="Taylor">Peggy Taylor</name>
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<author><name sortKey="Pan, Sarah" sort="Pan, Sarah" uniqKey="Pan S" first="Sarah" last="Pan">Sarah Pan</name>
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<author><name sortKey="Frasier, Mark" sort="Frasier, Mark" uniqKey="Frasier M" first="Mark" last="Frasier">Mark Frasier</name>
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<author><name sortKey="Marek, Kenneth" sort="Marek, Kenneth" uniqKey="Marek K" first="Kenneth" last="Marek">Kenneth Marek</name>
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<author><name sortKey="Kieburtz, Karl" sort="Kieburtz, Karl" uniqKey="Kieburtz K" first="Karl" last="Kieburtz">Karl Kieburtz</name>
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<country xml:lang="fr">États-Unis</country>
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</placeName>
<wicri:cityArea>Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester</wicri:cityArea>
</affiliation>
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</placeName>
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<author><name sortKey="Jennings, Danna" sort="Jennings, Danna" uniqKey="Jennings D" first="Danna" last="Jennings">Danna Jennings</name>
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<author><name sortKey="Simuni, Tanya" sort="Simuni, Tanya" uniqKey="Simuni T" first="Tanya" last="Simuni">Tanya Simuni</name>
<affiliation wicri:level="2"><nlm:aff id="A12">Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Illinois</region>
</placeName>
<wicri:cityArea>Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Tanner, Caroline M" sort="Tanner, Caroline M" uniqKey="Tanner C" first="Caroline" last="Tanner">Caroline Tanner</name>
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<placeName><region type="state">Californie</region>
</placeName>
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<author><name sortKey="Singleton, Andrew" sort="Singleton, Andrew" uniqKey="Singleton A" first="Andrew" last="Singleton">Andrew Singleton</name>
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<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Toga, Arthur W" sort="Toga, Arthur W" uniqKey="Toga A" first="Arthur" last="Toga">Arthur Toga</name>
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</affiliation>
</author>
<author><name sortKey="Chowdhury, Sohini" sort="Chowdhury, Sohini" uniqKey="Chowdhury S" first="Sohini" last="Chowdhury">Sohini Chowdhury</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>The Michael J. Fox Foundation for Parkinson’s Research, New York</wicri:cityArea>
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<author><name sortKey="Mollenhauer, Brit" sort="Mollenhauer, Brit" uniqKey="Mollenhauer B" first="Brit" last="Mollenhauer">Brit Mollenhauer</name>
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<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Neurosurgery and Neuropathology, University of Goettingen, Goettingen</wicri:regionArea>
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<wicri:noRegion>Goettingen</wicri:noRegion>
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<author><name sortKey="Trojanowski, John Q" sort="Trojanowski, John Q" uniqKey="Trojanowski J" first="John" last="Trojanowski">John Trojanowski</name>
<affiliation><nlm:aff id="A1">Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia</nlm:aff>
<wicri:noCountry code="subfield">Philadelphia</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A4">Morris K. Udall Center of Excellence for Parkinson’s Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia</nlm:aff>
<wicri:noCountry code="subfield">Philadelphia</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A18">Institute on Aging, Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia</nlm:aff>
<wicri:noCountry code="subfield">Philadelphia</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Shaw, Leslie M" sort="Shaw, Leslie M" uniqKey="Shaw L" first="Leslie" last="Shaw">Leslie Shaw</name>
<affiliation><nlm:aff id="A1">Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia</nlm:aff>
<wicri:noCountry code="subfield">Philadelphia</wicri:noCountry>
</affiliation>
</author>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Association of Cerebrospinal Fluid β-Amyloid 1-42, T-tau, P-tau<sub>181</sub>
, and α-Synuclein Levels With Clinical Features of Drug-Naive Patients With Early Parkinson Disease</title>
<author><name sortKey="Kang, Ju Hee" sort="Kang, Ju Hee" uniqKey="Kang J" first="Ju" last="Kang">Ju Kang</name>
<affiliation><nlm:aff id="A1">Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia</nlm:aff>
<wicri:noCountry code="subfield">Philadelphia</wicri:noCountry>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A2">Department of Pharmacology, Inha University School of Medicine, Incheon, Republic of Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>Department of Pharmacology, Inha University School of Medicine, Incheon</wicri:regionArea>
<wicri:noRegion>Incheon</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Irwin, David J" sort="Irwin, David J" uniqKey="Irwin D" first="David" last="Irwin">David Irwin</name>
<affiliation><nlm:aff id="A3">Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia</nlm:aff>
<wicri:noCountry code="subfield">Philadelphia</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A4">Morris K. Udall Center of Excellence for Parkinson’s Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia</nlm:aff>
<wicri:noCountry code="subfield">Philadelphia</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Chen Plotkin, Alice S" sort="Chen Plotkin, Alice S" uniqKey="Chen Plotkin A" first="Alice" last="Chen">Alice Chen</name>
<affiliation><nlm:aff id="A3">Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia</nlm:aff>
<wicri:noCountry code="subfield">Philadelphia</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A4">Morris K. Udall Center of Excellence for Parkinson’s Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia</nlm:aff>
<wicri:noCountry code="subfield">Philadelphia</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Siderowf, Andrew" sort="Siderowf, Andrew" uniqKey="Siderowf A" first="Andrew" last="Siderowf">Andrew Siderowf</name>
<affiliation wicri:level="2"><nlm:aff id="A5">Avid Radiopharmaceuticals, Philadelphia, Pennsylvania</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Avid Radiopharmaceuticals, Philadelphia</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Caspell, Chelsea" sort="Caspell, Chelsea" uniqKey="Caspell C" first="Chelsea" last="Caspell">Chelsea Caspell</name>
<affiliation><nlm:aff id="A6">Department of Biostatistics, College of Public Health, University of Iowa, Iowa City</nlm:aff>
<wicri:noCountry code="subfield">Iowa City</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Coffey, Christopher S" sort="Coffey, Christopher S" uniqKey="Coffey C" first="Christopher" last="Coffey">Christopher Coffey</name>
<affiliation><nlm:aff id="A6">Department of Biostatistics, College of Public Health, University of Iowa, Iowa City</nlm:aff>
<wicri:noCountry code="subfield">Iowa City</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Walig Rska, Teresa" sort="Walig Rska, Teresa" uniqKey="Walig Rska T" first="Teresa" last="Walig">Teresa Walig</name>
<affiliation><nlm:aff id="A1">Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia</nlm:aff>
<wicri:noCountry code="subfield">Philadelphia</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Taylor, Peggy" sort="Taylor, Peggy" uniqKey="Taylor P" first="Peggy" last="Taylor">Peggy Taylor</name>
<affiliation wicri:level="2"><nlm:aff id="A7">Covance Inc, Dedham, Massachusetts</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Covance Inc, Dedham</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Pan, Sarah" sort="Pan, Sarah" uniqKey="Pan S" first="Sarah" last="Pan">Sarah Pan</name>
<affiliation><nlm:aff id="A1">Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia</nlm:aff>
<wicri:noCountry code="subfield">Philadelphia</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Frasier, Mark" sort="Frasier, Mark" uniqKey="Frasier M" first="Mark" last="Frasier">Mark Frasier</name>
<affiliation wicri:level="2"><nlm:aff id="A8">The Michael J. Fox Foundation for Parkinson’s Research, New York, New York</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>The Michael J. Fox Foundation for Parkinson’s Research, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Marek, Kenneth" sort="Marek, Kenneth" uniqKey="Marek K" first="Kenneth" last="Marek">Kenneth Marek</name>
<affiliation wicri:level="2"><nlm:aff id="A9">Institute for Neurodegenerative Disorders, New Haven, Connecticut</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Connecticut</region>
</placeName>
<wicri:cityArea>Institute for Neurodegenerative Disorders, New Haven</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Kieburtz, Karl" sort="Kieburtz, Karl" uniqKey="Kieburtz K" first="Karl" last="Kieburtz">Karl Kieburtz</name>
<affiliation wicri:level="2"><nlm:aff id="A10">Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, New York</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A11">Clinical Trials Coordination Center, University of Rochester, Rochester, New York</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Clinical Trials Coordination Center, University of Rochester, Rochester</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Jennings, Danna" sort="Jennings, Danna" uniqKey="Jennings D" first="Danna" last="Jennings">Danna Jennings</name>
<affiliation wicri:level="2"><nlm:aff id="A9">Institute for Neurodegenerative Disorders, New Haven, Connecticut</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Connecticut</region>
</placeName>
<wicri:cityArea>Institute for Neurodegenerative Disorders, New Haven</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Simuni, Tanya" sort="Simuni, Tanya" uniqKey="Simuni T" first="Tanya" last="Simuni">Tanya Simuni</name>
<affiliation wicri:level="2"><nlm:aff id="A12">Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Illinois</region>
</placeName>
<wicri:cityArea>Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Tanner, Caroline M" sort="Tanner, Caroline M" uniqKey="Tanner C" first="Caroline" last="Tanner">Caroline Tanner</name>
<affiliation wicri:level="2"><nlm:aff id="A13">Parkinson’s Institute, Sunnyvale, California</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Parkinson’s Institute, Sunnyvale</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Singleton, Andrew" sort="Singleton, Andrew" uniqKey="Singleton A" first="Andrew" last="Singleton">Andrew Singleton</name>
<affiliation wicri:level="2"><nlm:aff id="A14">Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Toga, Arthur W" sort="Toga, Arthur W" uniqKey="Toga A" first="Arthur" last="Toga">Arthur Toga</name>
<affiliation wicri:level="3"><nlm:aff id="A15">Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles</nlm:aff>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
<wicri:orgArea>Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine, University of California</wicri:orgArea>
</affiliation>
</author>
<author><name sortKey="Chowdhury, Sohini" sort="Chowdhury, Sohini" uniqKey="Chowdhury S" first="Sohini" last="Chowdhury">Sohini Chowdhury</name>
<affiliation wicri:level="2"><nlm:aff id="A8">The Michael J. Fox Foundation for Parkinson’s Research, New York, New York</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>The Michael J. Fox Foundation for Parkinson’s Research, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Mollenhauer, Brit" sort="Mollenhauer, Brit" uniqKey="Mollenhauer B" first="Brit" last="Mollenhauer">Brit Mollenhauer</name>
<affiliation wicri:level="3"><nlm:aff id="A16">Paracelsus-Elena-Klinik, Kassel, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Paracelsus-Elena-Klinik, Kassel</wicri:regionArea>
<placeName><region type="land" nuts="1">Hesse (Land)</region>
<region type="district" nuts="2">District de Kassel</region>
<settlement type="city">Cassel (Hesse)</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A17">Department of Neurosurgery and Neuropathology, University of Goettingen, Goettingen, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Neurosurgery and Neuropathology, University of Goettingen, Goettingen</wicri:regionArea>
<wicri:noRegion>Goettingen</wicri:noRegion>
<wicri:noRegion>Goettingen</wicri:noRegion>
<wicri:noRegion>Goettingen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Trojanowski, John Q" sort="Trojanowski, John Q" uniqKey="Trojanowski J" first="John" last="Trojanowski">John Trojanowski</name>
<affiliation><nlm:aff id="A1">Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia</nlm:aff>
<wicri:noCountry code="subfield">Philadelphia</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A4">Morris K. Udall Center of Excellence for Parkinson’s Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia</nlm:aff>
<wicri:noCountry code="subfield">Philadelphia</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="A18">Institute on Aging, Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia</nlm:aff>
<wicri:noCountry code="subfield">Philadelphia</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Shaw, Leslie M" sort="Shaw, Leslie M" uniqKey="Shaw L" first="Leslie" last="Shaw">Leslie Shaw</name>
<affiliation><nlm:aff id="A1">Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia</nlm:aff>
<wicri:noCountry code="subfield">Philadelphia</wicri:noCountry>
</affiliation>
</author>
</analytic>
<series><title level="j">JAMA neurology</title>
<idno type="ISSN">2168-6149</idno>
<idno type="e-ISSN">2168-6157</idno>
<imprint><date when="2013">2013</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amyloid beta-Peptides (cerebrospinal fluid)</term>
<term>Case-Control Studies</term>
<term>Cohort Studies</term>
<term>Female</term>
<term>Humans</term>
<term>Male</term>
<term>Memory (physiology)</term>
<term>Middle Aged</term>
<term>Movement (physiology)</term>
<term>Neuropsychological Tests</term>
<term>Parkinson Disease (cerebrospinal fluid)</term>
<term>Parkinson Disease (physiopathology)</term>
<term>Peptide Fragments (cerebrospinal fluid)</term>
<term>Phosphorylation</term>
<term>Regression Analysis</term>
<term>Severity of Illness Index</term>
<term>Statistics as Topic</term>
<term>Threonine (metabolism)</term>
<term>Verbal Learning (physiology)</term>
<term>alpha-Synuclein (cerebrospinal fluid)</term>
<term>tau Proteins (cerebrospinal fluid)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="cerebrospinal fluid" xml:lang="en"><term>Amyloid beta-Peptides</term>
<term>Peptide Fragments</term>
<term>alpha-Synuclein</term>
<term>tau Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="cerebrospinal fluid" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Threonine</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Memory</term>
<term>Movement</term>
<term>Verbal Learning</term>
</keywords>
<keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Case-Control Studies</term>
<term>Cohort Studies</term>
<term>Female</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Neuropsychological Tests</term>
<term>Phosphorylation</term>
<term>Regression Analysis</term>
<term>Severity of Illness Index</term>
<term>Statistics as Topic</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Importance</title>
<p id="P1">We observed a significant correlation between cerebrospinal fluid (CSF) levels of tau proteins and α-synuclein, but not β-amyloid 1–42 (Aβ1–42), and lower concentration of CSF biomarkers, as compared with healthy controls, in a cohort of entirely untreated patients with Parkinson disease (PD) at the earliest stage of the disease studied so far.</p>
</sec>
<sec id="S2"><title>Objective</title>
<p id="P2">To evaluate the baseline characteristics and relationship to clinical features of CSF biomarkers (Aβ1–42, total tau [T-tau], tau phosphorylated at threonine 181 [P-tau<sub>181</sub>
], and α-synuclein) in drug-naive patients with early PD and demographically matched healthy controls enrolled in the Parkinson’s Progression Markers Initiative (PPMI) study.</p>
</sec>
<sec id="S3"><title>Design, Setting, and Participants</title>
<p id="P3">Cross-sectional study of the initial 102 research volunteers (63 patients with PD and 39 healthy controls) of the PPMI cohort.</p>
</sec>
<sec id="S4"><title>Main Outcomes and Measures</title>
<p id="P4">The CSF biomarkers were measured by INNO-BIA AlzBio3 immunoassay (Aβ1–42, T-tau, and P-tau<sub>181</sub>
; Innogenetics Inc) or by enzyme-linked immunosorbent assay (α-synuclein). Clinical features including diagnosis, demographic characteristics, motor, neuropsychiatric, and cognitive assessments, and DaTscan were systematically assessed according to the PPMI study protocol.</p>
</sec>
<sec id="S5"><title>Results</title>
<p id="P5">Slightly, but significantly, lower levels of Aβ1–42, T-tau, P-tau<sub>181</sub>
, α-synuclein, and T-tau/Aβ1–42 were seen in subjects with PD compared with healthy controls but with a marked overlap between groups. Using multivariate regression analysis, we found that lower Aβ1–42 and P-tau<sub>181</sub>
levels were associated with PD diagnosis and that decreased CSF T-tau and α-synuclein were associated with increased motor severity. Notably, when we classified patients with PD by their motor phenotypes, lower CSF Aβ1–42 and P-tau<sub>181</sub>
concentrations were associated with the postural instability–gait disturbance–dominant phenotype but not with the tremor-dominant or intermediate phenotype. Finally, we found a significant correlation of the levels of α-synuclein with the levels of T-tau and P-tau<sub>181</sub>
.</p>
</sec>
<sec id="S6"><title>Conclusions and Relevance</title>
<p id="P6">In this first report of CSF biomarkers in PPMI study subjects, we found that measures of CSF Aβ1–42, T-tau, P-tau<sub>181</sub>
, and α-synuclein have prognostic and diagnostic potential in early-stage PD. Further investigations using the entire PPMI cohort will test the predictive performance of CSF biomarkers for PD progression.</p>
</sec>
</div>
</front>
</TEI>
<affiliations><list><country><li>Allemagne</li>
<li>Corée du Sud</li>
<li>États-Unis</li>
</country>
<region><li>Californie</li>
<li>Connecticut</li>
<li>District de Kassel</li>
<li>Hesse (Land)</li>
<li>Illinois</li>
<li>Maryland</li>
<li>Massachusetts</li>
<li>Pennsylvanie</li>
<li>État de New York</li>
</region>
<settlement><li>Cassel (Hesse)</li>
<li>Los Angeles</li>
</settlement>
</list>
<tree><noCountry><name sortKey="Caspell, Chelsea" sort="Caspell, Chelsea" uniqKey="Caspell C" first="Chelsea" last="Caspell">Chelsea Caspell</name>
<name sortKey="Chen Plotkin, Alice S" sort="Chen Plotkin, Alice S" uniqKey="Chen Plotkin A" first="Alice" last="Chen">Alice Chen</name>
<name sortKey="Coffey, Christopher S" sort="Coffey, Christopher S" uniqKey="Coffey C" first="Christopher" last="Coffey">Christopher Coffey</name>
<name sortKey="Irwin, David J" sort="Irwin, David J" uniqKey="Irwin D" first="David" last="Irwin">David Irwin</name>
<name sortKey="Pan, Sarah" sort="Pan, Sarah" uniqKey="Pan S" first="Sarah" last="Pan">Sarah Pan</name>
<name sortKey="Shaw, Leslie M" sort="Shaw, Leslie M" uniqKey="Shaw L" first="Leslie" last="Shaw">Leslie Shaw</name>
<name sortKey="Trojanowski, John Q" sort="Trojanowski, John Q" uniqKey="Trojanowski J" first="John" last="Trojanowski">John Trojanowski</name>
<name sortKey="Walig Rska, Teresa" sort="Walig Rska, Teresa" uniqKey="Walig Rska T" first="Teresa" last="Walig">Teresa Walig</name>
</noCountry>
<country name="Corée du Sud"><noRegion><name sortKey="Kang, Ju Hee" sort="Kang, Ju Hee" uniqKey="Kang J" first="Ju" last="Kang">Ju Kang</name>
</noRegion>
</country>
<country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Siderowf, Andrew" sort="Siderowf, Andrew" uniqKey="Siderowf A" first="Andrew" last="Siderowf">Andrew Siderowf</name>
</region>
<name sortKey="Chowdhury, Sohini" sort="Chowdhury, Sohini" uniqKey="Chowdhury S" first="Sohini" last="Chowdhury">Sohini Chowdhury</name>
<name sortKey="Frasier, Mark" sort="Frasier, Mark" uniqKey="Frasier M" first="Mark" last="Frasier">Mark Frasier</name>
<name sortKey="Jennings, Danna" sort="Jennings, Danna" uniqKey="Jennings D" first="Danna" last="Jennings">Danna Jennings</name>
<name sortKey="Kieburtz, Karl" sort="Kieburtz, Karl" uniqKey="Kieburtz K" first="Karl" last="Kieburtz">Karl Kieburtz</name>
<name sortKey="Kieburtz, Karl" sort="Kieburtz, Karl" uniqKey="Kieburtz K" first="Karl" last="Kieburtz">Karl Kieburtz</name>
<name sortKey="Marek, Kenneth" sort="Marek, Kenneth" uniqKey="Marek K" first="Kenneth" last="Marek">Kenneth Marek</name>
<name sortKey="Simuni, Tanya" sort="Simuni, Tanya" uniqKey="Simuni T" first="Tanya" last="Simuni">Tanya Simuni</name>
<name sortKey="Singleton, Andrew" sort="Singleton, Andrew" uniqKey="Singleton A" first="Andrew" last="Singleton">Andrew Singleton</name>
<name sortKey="Tanner, Caroline M" sort="Tanner, Caroline M" uniqKey="Tanner C" first="Caroline" last="Tanner">Caroline Tanner</name>
<name sortKey="Taylor, Peggy" sort="Taylor, Peggy" uniqKey="Taylor P" first="Peggy" last="Taylor">Peggy Taylor</name>
<name sortKey="Toga, Arthur W" sort="Toga, Arthur W" uniqKey="Toga A" first="Arthur" last="Toga">Arthur Toga</name>
</country>
<country name="Allemagne"><region name="Hesse (Land)"><name sortKey="Mollenhauer, Brit" sort="Mollenhauer, Brit" uniqKey="Mollenhauer B" first="Brit" last="Mollenhauer">Brit Mollenhauer</name>
</region>
<name sortKey="Mollenhauer, Brit" sort="Mollenhauer, Brit" uniqKey="Mollenhauer B" first="Brit" last="Mollenhauer">Brit Mollenhauer</name>
</country>
</tree>
</affiliations>
</record>
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