Direct quantification of CSF α-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration
Identifieur interne : 002407 ( Main/Exploration ); précédent : 002406; suivant : 002408Direct quantification of CSF α-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration
Auteurs : Brit Mollenhauer [États-Unis] ; Valerie Cullen [États-Unis] ; Ilana Kahn [États-Unis] ; Bryan Krastins [États-Unis] ; Tiago F. Outeiro [États-Unis] ; Imelda Pepivani [États-Unis] ; Juliana Ng [Canada] ; Walter Schulz-Schaeffer [Allemagne] ; Hans A. Kretzschmar [Allemagne] ; Pamela J. Mclean [États-Unis] ; Claudia Trenkwalder [Allemagne] ; David A. Sarracino [États-Unis] ; Jean-Paul Vonsattel [États-Unis] ; Joseph J. Locascio [États-Unis] ; Omar M. A. El-Agnaf [Émirats arabes unis] ; Michael G. Schlossmacher [États-Unis, Canada]Source :
- Experimental neurology : (Print) [ 0014-4886 ] ; 2008.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
Abstract
Because accumulation of α-synuclein (αS) in the brain is a hallmark of Parkinson disease (PD) and related disorders, we examined its occurrence in human cerebrospinal fluid (CSF). Following affinity enrichment and trypsin digestion of CSF collected from a neurologically healthy donor, we identified several aS-derived peptides by mass spectrometry. The concentration of aS amounted to <0.001% of the CSF proteome. We then built, validated and optimized a sandwich-type, enzyme-linked immunoadsorbent assay (ELISA) to measure total aS levels in unconcentrated CSF. In a cross-sectional study of 100 living donors, we examined cell-free CSF samples from subjects clinically diagnosed with advanced PD, dementia with Lewy bodies (DLB), Alzheimer disease (AD), and a group of non-neurodegenerative disease controls (NCO). In these four groups the CSF aS concentrations ranged from 0.8 to 16.2 pg/μl. Mean CSF aS values were lower in donors with a primary synucleinopathy (PD, DLB: n=57) than in the other two groups (AD, NCO: n=35; p=0.025). By contrast, living Creutzfeldt-Jakob disease patients showed markedly elevated CSF αS levels (n=8; mean, 300 pg/μl; p<0.001). Our results unequivocally confirm the presence of aS in adult human CSF. In a first feasibility study employing a novel ELISA, we found relatively low CSF aS concentrations in subjects with parkinsonism linked to synucleinopathy, PD and DLB. In definite prion disease cases, we recorded a marked rise in total CSF aS resulting from rapid cell death. Our results will likely aid future biomarker explorations in neurodegenerative conditions and facilitate target validation studies.
Affiliations:
- Allemagne, Canada, Émirats arabes unis, États-Unis
- District de Kassel, Hesse (Land), Massachusetts, État de New York
- Boston, Cassel (Hesse), New York
- Université Columbia
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Outeiro</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Neurology. Massachusetts General Hospital, Harvard Medical School</s1><s2>Boston</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Boston</settlement><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Pepivani, Imelda" sort="Pepivani, Imelda" uniqKey="Pepivani I" first="Imelda" last="Pepivani">Imelda Pepivani</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School</s1><s2>Boston</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Boston</settlement><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Ng, Juliana" sort="Ng, Juliana" uniqKey="Ng J" first="Juliana" last="Ng">Juliana Ng</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Division of Neuroscience, Ottawa Health Research Institute, University of Ottawa</s1><s2>Ontario</s2><s3>CAN</s3><sZ>7 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Schulz Schaeffer, Walter" sort="Schulz Schaeffer, Walter" uniqKey="Schulz Schaeffer W" first="Walter" last="Schulz-Schaeffer">Walter Schulz-Schaeffer</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Neuropathology, Georg-August University Goettingen</s1><s2>Goettingen</s2><s3>DEU</s3><sZ>8 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Goettingen</wicri:noRegion><wicri:noRegion>Georg-August University Goettingen</wicri:noRegion><wicri:noRegion>Goettingen</wicri:noRegion></affiliation></author><author><name sortKey="Kretzschmar, Hans A" sort="Kretzschmar, Hans A" uniqKey="Kretzschmar H" first="Hans A." last="Kretzschmar">Hans A. Kretzschmar</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Department of Pathology, Ludwig Maximilians University Munich</s1><s3>DEU</s3><sZ>9 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Ludwig Maximilians University Munich</wicri:noRegion><wicri:noRegion>Department of Pathology, Ludwig Maximilians University Munich</wicri:noRegion></affiliation></author><author><name sortKey="Mclean, Pamela J" sort="Mclean, Pamela J" uniqKey="Mclean P" first="Pamela J." last="Mclean">Pamela J. Mclean</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Neurology. Massachusetts General Hospital, Harvard Medical School</s1><s2>Boston</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Boston</settlement><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Trenkwalder, Claudia" sort="Trenkwalder, Claudia" uniqKey="Trenkwalder C" first="Claudia" last="Trenkwalder">Claudia Trenkwalder</name><affiliation wicri:level="3"><inist:fA14 i1="07"><s1>Paracelsus-Elena Klinik, Georg-August University Goettingen</s1><s2>Kassel</s2><s3>DEU</s3><sZ>11 aut.</sZ></inist:fA14><country>Allemagne</country><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></author><author><name sortKey="Sarracino, David A" sort="Sarracino, David A" uniqKey="Sarracino D" first="David A." last="Sarracino">David A. Sarracino</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Proteomic Core Facility, Brigham and Women's Hospital, Harvard Medical School</s1><s2>Cambridge</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Cambridge</wicri:noRegion></affiliation></author><author><name sortKey="Vonsattel, Jean Paul" sort="Vonsattel, Jean Paul" uniqKey="Vonsattel J" first="Jean-Paul" last="Vonsattel">Jean-Paul Vonsattel</name><affiliation wicri:level="4"><inist:fA14 i1="08"><s1>Institute of Pathology, Columbia University</s1><s2>New York</s2><s3>USA</s3><sZ>13 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region><settlement type="city">New York</settlement></placeName><orgName type="university">Université Columbia</orgName></affiliation></author><author><name sortKey="Locascio, Joseph J" sort="Locascio, Joseph J" uniqKey="Locascio J" first="Joseph J." last="Locascio">Joseph J. Locascio</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Neurology. Massachusetts General Hospital, Harvard Medical School</s1><s2>Boston</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Boston</settlement><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="El Agnaf, Omar M A" sort="El Agnaf, Omar M A" uniqKey="El Agnaf O" first="Omar M. A." last="El-Agnaf">Omar M. A. El-Agnaf</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University</s1><s2>Al Ain</s2><s3>ARE</s3><sZ>15 aut.</sZ></inist:fA14><country>Émirats arabes unis</country><wicri:noRegion>Al Ain</wicri:noRegion></affiliation></author><author><name sortKey="Schlossmacher, Michael G" sort="Schlossmacher, Michael G" uniqKey="Schlossmacher M" first="Michael G." last="Schlossmacher">Michael G. Schlossmacher</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School</s1><s2>Boston</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Boston</settlement><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Division of Neuroscience, Ottawa Health Research Institute, University of Ottawa</s1><s2>Ontario</s2><s3>CAN</s3><sZ>7 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">08-0519326</idno><date when="2008">2008</date><idno type="stanalyst">PASCAL 08-0519326 INIST</idno><idno type="RBID">Pascal:08-0519326</idno><idno type="wicri:Area/PascalFrancis/Corpus">000611</idno><idno type="wicri:Area/PascalFrancis/Curation">000699</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000555</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000555</idno><idno type="wicri:doubleKey">0014-4886:2008:Mollenhauer B:direct:quantification:of</idno><idno type="wicri:Area/Main/Merge">002616</idno><idno type="wicri:Area/Main/Curation">002407</idno><idno type="wicri:Area/Main/Exploration">002407</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Direct quantification of CSF α-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration</title><author><name sortKey="Mollenhauer, Brit" sort="Mollenhauer, Brit" uniqKey="Mollenhauer B" first="Brit" last="Mollenhauer">Brit Mollenhauer</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School</s1><s2>Boston</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Boston</settlement><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Cullen, Valerie" sort="Cullen, Valerie" uniqKey="Cullen V" first="Valerie" last="Cullen">Valerie Cullen</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School</s1><s2>Boston</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Boston</settlement><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Kahn, Ilana" sort="Kahn, Ilana" uniqKey="Kahn I" first="Ilana" last="Kahn">Ilana Kahn</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School</s1><s2>Boston</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Boston</settlement><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Krastins, Bryan" sort="Krastins, Bryan" uniqKey="Krastins B" first="Bryan" last="Krastins">Bryan Krastins</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Proteomic Core Facility, Brigham and Women's Hospital, Harvard Medical School</s1><s2>Cambridge</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Cambridge</wicri:noRegion></affiliation></author><author><name sortKey="Outeiro, Tiago F" sort="Outeiro, Tiago F" uniqKey="Outeiro T" first="Tiago F." last="Outeiro">Tiago F. Outeiro</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Neurology. Massachusetts General Hospital, Harvard Medical School</s1><s2>Boston</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Boston</settlement><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Pepivani, Imelda" sort="Pepivani, Imelda" uniqKey="Pepivani I" first="Imelda" last="Pepivani">Imelda Pepivani</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School</s1><s2>Boston</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Boston</settlement><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Ng, Juliana" sort="Ng, Juliana" uniqKey="Ng J" first="Juliana" last="Ng">Juliana Ng</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Division of Neuroscience, Ottawa Health Research Institute, University of Ottawa</s1><s2>Ontario</s2><s3>CAN</s3><sZ>7 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Schulz Schaeffer, Walter" sort="Schulz Schaeffer, Walter" uniqKey="Schulz Schaeffer W" first="Walter" last="Schulz-Schaeffer">Walter Schulz-Schaeffer</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Neuropathology, Georg-August University Goettingen</s1><s2>Goettingen</s2><s3>DEU</s3><sZ>8 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Goettingen</wicri:noRegion><wicri:noRegion>Georg-August University Goettingen</wicri:noRegion><wicri:noRegion>Goettingen</wicri:noRegion></affiliation></author><author><name sortKey="Kretzschmar, Hans A" sort="Kretzschmar, Hans A" uniqKey="Kretzschmar H" first="Hans A." last="Kretzschmar">Hans A. Kretzschmar</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Department of Pathology, Ludwig Maximilians University Munich</s1><s3>DEU</s3><sZ>9 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Ludwig Maximilians University Munich</wicri:noRegion><wicri:noRegion>Department of Pathology, Ludwig Maximilians University Munich</wicri:noRegion></affiliation></author><author><name sortKey="Mclean, Pamela J" sort="Mclean, Pamela J" uniqKey="Mclean P" first="Pamela J." last="Mclean">Pamela J. Mclean</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Neurology. Massachusetts General Hospital, Harvard Medical School</s1><s2>Boston</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Boston</settlement><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Trenkwalder, Claudia" sort="Trenkwalder, Claudia" uniqKey="Trenkwalder C" first="Claudia" last="Trenkwalder">Claudia Trenkwalder</name><affiliation wicri:level="3"><inist:fA14 i1="07"><s1>Paracelsus-Elena Klinik, Georg-August University Goettingen</s1><s2>Kassel</s2><s3>DEU</s3><sZ>11 aut.</sZ></inist:fA14><country>Allemagne</country><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></author><author><name sortKey="Sarracino, David A" sort="Sarracino, David A" uniqKey="Sarracino D" first="David A." last="Sarracino">David A. Sarracino</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Proteomic Core Facility, Brigham and Women's Hospital, Harvard Medical School</s1><s2>Cambridge</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Cambridge</wicri:noRegion></affiliation></author><author><name sortKey="Vonsattel, Jean Paul" sort="Vonsattel, Jean Paul" uniqKey="Vonsattel J" first="Jean-Paul" last="Vonsattel">Jean-Paul Vonsattel</name><affiliation wicri:level="4"><inist:fA14 i1="08"><s1>Institute of Pathology, Columbia University</s1><s2>New York</s2><s3>USA</s3><sZ>13 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">État de New York</region><settlement type="city">New York</settlement></placeName><orgName type="university">Université Columbia</orgName></affiliation></author><author><name sortKey="Locascio, Joseph J" sort="Locascio, Joseph J" uniqKey="Locascio J" first="Joseph J." last="Locascio">Joseph J. Locascio</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Neurology. Massachusetts General Hospital, Harvard Medical School</s1><s2>Boston</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Boston</settlement><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="El Agnaf, Omar M A" sort="El Agnaf, Omar M A" uniqKey="El Agnaf O" first="Omar M. A." last="El-Agnaf">Omar M. A. El-Agnaf</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University</s1><s2>Al Ain</s2><s3>ARE</s3><sZ>15 aut.</sZ></inist:fA14><country>Émirats arabes unis</country><wicri:noRegion>Al Ain</wicri:noRegion></affiliation></author><author><name sortKey="Schlossmacher, Michael G" sort="Schlossmacher, Michael G" uniqKey="Schlossmacher M" first="Michael G." last="Schlossmacher">Michael G. Schlossmacher</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School</s1><s2>Boston</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Boston</settlement><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Division of Neuroscience, Ottawa Health Research Institute, University of Ottawa</s1><s2>Ontario</s2><s3>CAN</s3><sZ>7 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Experimental neurology : (Print)</title><title level="j" type="abbreviated">Exp. neurol. : (Print)</title><idno type="ISSN">0014-4886</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Experimental neurology : (Print)</title><title level="j" type="abbreviated">Exp. neurol. : (Print)</title><idno type="ISSN">0014-4886</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cerebrospinal fluid</term><term>Cross sectional study</term><term>Dementia</term><term>ELISA assay</term><term>Human</term><term>Mass spectrometry</term><term>Nervous system diseases</term><term>Parkinsonism</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Parkinsonisme</term><term>Démence</term><term>Pathologie du système nerveux</term><term>Liquide céphalorachidien</term><term>Technique ELISA</term><term>Etude transversale</term><term>Homme</term><term>Spectrométrie masse</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Because accumulation of α-synuclein (αS) in the brain is a hallmark of Parkinson disease (PD) and related disorders, we examined its occurrence in human cerebrospinal fluid (CSF). Following affinity enrichment and trypsin digestion of CSF collected from a neurologically healthy donor, we identified several aS-derived peptides by mass spectrometry. The concentration of aS amounted to <0.001% of the CSF proteome. We then built, validated and optimized a sandwich-type, enzyme-linked immunoadsorbent assay (ELISA) to measure total aS levels in unconcentrated CSF. In a cross-sectional study of 100 living donors, we examined cell-free CSF samples from subjects clinically diagnosed with advanced PD, dementia with Lewy bodies (DLB), Alzheimer disease (AD), and a group of non-neurodegenerative disease controls (NCO). In these four groups the CSF aS concentrations ranged from 0.8 to 16.2 pg/μl. Mean CSF aS values were lower in donors with a primary synucleinopathy (PD, DLB: n=57) than in the other two groups (AD, NCO: n=35; p=0.025). By contrast, living Creutzfeldt-Jakob disease patients showed markedly elevated CSF αS levels (n=8; mean, 300 pg/μl; p<0.001). Our results unequivocally confirm the presence of aS in adult human CSF. In a first feasibility study employing a novel ELISA, we found relatively low CSF aS concentrations in subjects with parkinsonism linked to synucleinopathy, PD and DLB. In definite prion disease cases, we recorded a marked rise in total CSF aS resulting from rapid cell death. Our results will likely aid future biomarker explorations in neurodegenerative conditions and facilitate target validation studies.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Canada</li><li>Émirats arabes unis</li><li>États-Unis</li></country><region><li>District de Kassel</li><li>Hesse (Land)</li><li>Massachusetts</li><li>État de New York</li></region><settlement><li>Boston</li><li>Cassel (Hesse)</li><li>New York</li></settlement><orgName><li>Université Columbia</li></orgName></list><tree><country name="États-Unis"><region name="Massachusetts"><name sortKey="Mollenhauer, Brit" sort="Mollenhauer, Brit" uniqKey="Mollenhauer B" first="Brit" last="Mollenhauer">Brit Mollenhauer</name></region><name sortKey="Cullen, Valerie" sort="Cullen, Valerie" uniqKey="Cullen V" first="Valerie" last="Cullen">Valerie Cullen</name><name sortKey="Kahn, Ilana" sort="Kahn, Ilana" uniqKey="Kahn I" first="Ilana" last="Kahn">Ilana Kahn</name><name sortKey="Krastins, Bryan" sort="Krastins, Bryan" uniqKey="Krastins B" first="Bryan" last="Krastins">Bryan Krastins</name><name sortKey="Locascio, Joseph J" sort="Locascio, Joseph J" uniqKey="Locascio J" first="Joseph J." last="Locascio">Joseph J. Locascio</name><name sortKey="Mclean, Pamela J" sort="Mclean, Pamela J" uniqKey="Mclean P" first="Pamela J." last="Mclean">Pamela J. Mclean</name><name sortKey="Outeiro, Tiago F" sort="Outeiro, Tiago F" uniqKey="Outeiro T" first="Tiago F." last="Outeiro">Tiago F. Outeiro</name><name sortKey="Pepivani, Imelda" sort="Pepivani, Imelda" uniqKey="Pepivani I" first="Imelda" last="Pepivani">Imelda Pepivani</name><name sortKey="Sarracino, David A" sort="Sarracino, David A" uniqKey="Sarracino D" first="David A." last="Sarracino">David A. Sarracino</name><name sortKey="Schlossmacher, Michael G" sort="Schlossmacher, Michael G" uniqKey="Schlossmacher M" first="Michael G." last="Schlossmacher">Michael G. Schlossmacher</name><name sortKey="Vonsattel, Jean Paul" sort="Vonsattel, Jean Paul" uniqKey="Vonsattel J" first="Jean-Paul" last="Vonsattel">Jean-Paul Vonsattel</name></country><country name="Canada"><noRegion><name sortKey="Ng, Juliana" sort="Ng, Juliana" uniqKey="Ng J" first="Juliana" last="Ng">Juliana Ng</name></noRegion><name sortKey="Schlossmacher, Michael G" sort="Schlossmacher, Michael G" uniqKey="Schlossmacher M" first="Michael G." last="Schlossmacher">Michael G. Schlossmacher</name></country><country name="Allemagne"><noRegion><name sortKey="Schulz Schaeffer, Walter" sort="Schulz Schaeffer, Walter" uniqKey="Schulz Schaeffer W" first="Walter" last="Schulz-Schaeffer">Walter Schulz-Schaeffer</name></noRegion><name sortKey="Kretzschmar, Hans A" sort="Kretzschmar, Hans A" uniqKey="Kretzschmar H" first="Hans A." last="Kretzschmar">Hans A. Kretzschmar</name><name sortKey="Trenkwalder, Claudia" sort="Trenkwalder, Claudia" uniqKey="Trenkwalder C" first="Claudia" last="Trenkwalder">Claudia Trenkwalder</name></country><country name="Émirats arabes unis"><noRegion><name sortKey="El Agnaf, Omar M A" sort="El Agnaf, Omar M A" uniqKey="El Agnaf O" first="Omar M. A." last="El-Agnaf">Omar M. A. El-Agnaf</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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