Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects
Identifieur interne : 002E47 ( Main/Corpus ); précédent : 002E46; suivant : 002E48Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects
Auteurs : Leslie M. Shaw ; Hugo Vanderstichele ; Malgorzata Knapik-Czajka ; Christopher M. Clark ; Paul S. Aisen ; Ronald C. Petersen ; Kaj Blennow ; Holly Soares ; Adam Simon ; Piotr Lewczuk ; Robert Dean ; Eric Siemers ; William Potter ; Virginia M. Lee ; John Q. TrojanowskiSource :
- Annals of Neurology [ 0364-5134 ] ; 2009-04.
Abstract
Objective: Develop a cerebrospinal fluid biomarker signature for mild Alzheimer's disease (AD) in Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects. Methods: Amyloid‐β 1 to 42 peptide (Aβ1–42), total tau (t‐tau), and tau phosphorylated at the threonine 181 were measured in (1) cerebrospinal fluid (CSF) samples obtained during baseline evaluation of 100 mild AD, 196 mild cognitive impairment, and 114 elderly cognitively normal (NC) subjects in ADNI; and (2) independent 56 autopsy‐confirmed AD cases and 52 age‐matched elderly NCs using a multiplex immunoassay. Detection of an AD CSF profile for t‐tau and Aβ1–42 in ADNI subjects was achieved using receiver operating characteristic cut points and logistic regression models derived from the autopsy‐confirmed CSF data. Results: CSF Aβ1–42 was the most sensitive biomarker for AD in the autopsy cohort of CSF samples: receiver operating characteristic area under the curve of 0.913 and sensitivity for AD detection of 96.4%. In the ADNI cohort, a logistic regression model for Aβ1–42, t‐tau, and APOε4 allele count provided the best assessment delineation of mild AD. An AD‐like baseline CSF profile for t‐tau/Aβ1–42 was detected in 33 of 37 ADNI mild cognitive impairment subjects who converted to probable AD during the first year of the study. Interpretation: The CSF biomarker signature of AD defined by Aβ1–42 and t‐tau in the autopsy‐confirmed AD cohort and confirmed in the cohort followed in ADNI for 12 months detects mild AD in a large, multisite, prospective clinical investigation, and this signature appears to predict conversion from mild cognitive impairment to AD. Ann Neurol 2009
Url:
DOI: 10.1002/ana.21610
Links to Exploration step
ISTEX:FF9CA806BB069C2D45DF06E71E5969BD9215758BLe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects</title><author><name sortKey="Shaw, Leslie M" sort="Shaw, Leslie M" uniqKey="Shaw L" first="Leslie M." last="Shaw">Leslie M. Shaw</name><affiliation><mods:affiliation>Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</mods:affiliation></affiliation></author><author><name sortKey="Vanderstichele, Hugo" sort="Vanderstichele, Hugo" uniqKey="Vanderstichele H" first="Hugo" last="Vanderstichele">Hugo Vanderstichele</name><affiliation><mods:affiliation>Department of Diagnostic Development, Innogenetics NV, Gent, Belgium</mods:affiliation></affiliation></author><author><name sortKey="Knapik Zajka, Malgorzata" sort="Knapik Zajka, Malgorzata" uniqKey="Knapik Zajka M" first="Malgorzata" last="Knapik-Czajka">Malgorzata Knapik-Czajka</name><affiliation><mods:affiliation>Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</mods:affiliation></affiliation></author><author><name sortKey="Clark, Christopher M" sort="Clark, Christopher M" uniqKey="Clark C" first="Christopher M." last="Clark">Christopher M. Clark</name><affiliation><mods:affiliation>Department of Neurology, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</mods:affiliation></affiliation></author><author><name sortKey="Aisen, Paul S" sort="Aisen, Paul S" uniqKey="Aisen P" first="Paul S." last="Aisen">Paul S. Aisen</name><affiliation><mods:affiliation>University of California San Diego, San Diego, CA</mods:affiliation></affiliation></author><author><name sortKey="Petersen, Ronald C" sort="Petersen, Ronald C" uniqKey="Petersen R" first="Ronald C." last="Petersen">Ronald C. Petersen</name><affiliation><mods:affiliation>Mayo Clinic College of Medicine, Rochester, MN</mods:affiliation></affiliation></author><author><name sortKey="Blennow, Kaj" sort="Blennow, Kaj" uniqKey="Blennow K" first="Kaj" last="Blennow">Kaj Blennow</name><affiliation><mods:affiliation>Department of Psychiatry and Neurochemistry, Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Göteborg University, Mölndal, Sweden</mods:affiliation></affiliation></author><author><name sortKey="Soares, Holly" sort="Soares, Holly" uniqKey="Soares H" first="Holly" last="Soares">Holly Soares</name><affiliation><mods:affiliation>Pfizer Global Research and Development, Groton, CT</mods:affiliation></affiliation></author><author><name sortKey="Simon, Adam" sort="Simon, Adam" uniqKey="Simon A" first="Adam" last="Simon">Adam Simon</name><affiliation><mods:affiliation>Merck Research Laboratories, West Point, PA</mods:affiliation></affiliation></author><author><name sortKey="Lewczuk, Piotr" sort="Lewczuk, Piotr" uniqKey="Lewczuk P" first="Piotr" last="Lewczuk">Piotr Lewczuk</name><affiliation><mods:affiliation>Department of Psychiatry and Psychotherapy, University of Erlangen‐Nuremberg, Erlangen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Dean, Robert" sort="Dean, Robert" uniqKey="Dean R" first="Robert" last="Dean">Robert Dean</name><affiliation><mods:affiliation>Eli Lilly & Company, Indianapolis, IN</mods:affiliation></affiliation></author><author><name sortKey="Siemers, Eric" sort="Siemers, Eric" uniqKey="Siemers E" first="Eric" last="Siemers">Eric Siemers</name><affiliation><mods:affiliation>Eli Lilly & Company, Indianapolis, IN</mods:affiliation></affiliation></author><author><name sortKey="Potter, William" sort="Potter, William" uniqKey="Potter W" first="William" last="Potter">William Potter</name><affiliation><mods:affiliation>Merck Research Laboratories, West Point, PA</mods:affiliation></affiliation></author><author><name sortKey="Lee, Virginia M" sort="Lee, Virginia M" uniqKey="Lee V" first="Virginia M." last="Lee">Virginia M. Lee</name><affiliation><mods:affiliation>Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</mods:affiliation></affiliation></author><author><name sortKey="Trojanowski, John Q" sort="Trojanowski, John Q" uniqKey="Trojanowski J" first="John Q." last="Trojanowski">John Q. Trojanowski</name><affiliation><mods:affiliation>Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:FF9CA806BB069C2D45DF06E71E5969BD9215758B</idno><date when="2009" year="2009">2009</date><idno type="doi">10.1002/ana.21610</idno><idno type="url">https://api.istex.fr/document/FF9CA806BB069C2D45DF06E71E5969BD9215758B/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">002E47</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects</title><author><name sortKey="Shaw, Leslie M" sort="Shaw, Leslie M" uniqKey="Shaw L" first="Leslie M." last="Shaw">Leslie M. Shaw</name><affiliation><mods:affiliation>Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</mods:affiliation></affiliation></author><author><name sortKey="Vanderstichele, Hugo" sort="Vanderstichele, Hugo" uniqKey="Vanderstichele H" first="Hugo" last="Vanderstichele">Hugo Vanderstichele</name><affiliation><mods:affiliation>Department of Diagnostic Development, Innogenetics NV, Gent, Belgium</mods:affiliation></affiliation></author><author><name sortKey="Knapik Zajka, Malgorzata" sort="Knapik Zajka, Malgorzata" uniqKey="Knapik Zajka M" first="Malgorzata" last="Knapik-Czajka">Malgorzata Knapik-Czajka</name><affiliation><mods:affiliation>Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</mods:affiliation></affiliation></author><author><name sortKey="Clark, Christopher M" sort="Clark, Christopher M" uniqKey="Clark C" first="Christopher M." last="Clark">Christopher M. Clark</name><affiliation><mods:affiliation>Department of Neurology, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</mods:affiliation></affiliation></author><author><name sortKey="Aisen, Paul S" sort="Aisen, Paul S" uniqKey="Aisen P" first="Paul S." last="Aisen">Paul S. Aisen</name><affiliation><mods:affiliation>University of California San Diego, San Diego, CA</mods:affiliation></affiliation></author><author><name sortKey="Petersen, Ronald C" sort="Petersen, Ronald C" uniqKey="Petersen R" first="Ronald C." last="Petersen">Ronald C. Petersen</name><affiliation><mods:affiliation>Mayo Clinic College of Medicine, Rochester, MN</mods:affiliation></affiliation></author><author><name sortKey="Blennow, Kaj" sort="Blennow, Kaj" uniqKey="Blennow K" first="Kaj" last="Blennow">Kaj Blennow</name><affiliation><mods:affiliation>Department of Psychiatry and Neurochemistry, Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Göteborg University, Mölndal, Sweden</mods:affiliation></affiliation></author><author><name sortKey="Soares, Holly" sort="Soares, Holly" uniqKey="Soares H" first="Holly" last="Soares">Holly Soares</name><affiliation><mods:affiliation>Pfizer Global Research and Development, Groton, CT</mods:affiliation></affiliation></author><author><name sortKey="Simon, Adam" sort="Simon, Adam" uniqKey="Simon A" first="Adam" last="Simon">Adam Simon</name><affiliation><mods:affiliation>Merck Research Laboratories, West Point, PA</mods:affiliation></affiliation></author><author><name sortKey="Lewczuk, Piotr" sort="Lewczuk, Piotr" uniqKey="Lewczuk P" first="Piotr" last="Lewczuk">Piotr Lewczuk</name><affiliation><mods:affiliation>Department of Psychiatry and Psychotherapy, University of Erlangen‐Nuremberg, Erlangen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Dean, Robert" sort="Dean, Robert" uniqKey="Dean R" first="Robert" last="Dean">Robert Dean</name><affiliation><mods:affiliation>Eli Lilly & Company, Indianapolis, IN</mods:affiliation></affiliation></author><author><name sortKey="Siemers, Eric" sort="Siemers, Eric" uniqKey="Siemers E" first="Eric" last="Siemers">Eric Siemers</name><affiliation><mods:affiliation>Eli Lilly & Company, Indianapolis, IN</mods:affiliation></affiliation></author><author><name sortKey="Potter, William" sort="Potter, William" uniqKey="Potter W" first="William" last="Potter">William Potter</name><affiliation><mods:affiliation>Merck Research Laboratories, West Point, PA</mods:affiliation></affiliation></author><author><name sortKey="Lee, Virginia M" sort="Lee, Virginia M" uniqKey="Lee V" first="Virginia M." last="Lee">Virginia M. Lee</name><affiliation><mods:affiliation>Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</mods:affiliation></affiliation></author><author><name sortKey="Trojanowski, John Q" sort="Trojanowski, John Q" uniqKey="Trojanowski J" first="John Q." last="Trojanowski">John Q. Trojanowski</name><affiliation><mods:affiliation>Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="ISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2009-04">2009-04</date><biblScope unit="volume">65</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="403">403</biblScope><biblScope unit="page" to="413">413</biblScope></imprint><idno type="ISSN">0364-5134</idno></series><idno type="istex">FF9CA806BB069C2D45DF06E71E5969BD9215758B</idno><idno type="DOI">10.1002/ana.21610</idno><idno type="ArticleID">ANA21610</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0364-5134</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Objective: Develop a cerebrospinal fluid biomarker signature for mild Alzheimer's disease (AD) in Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects. Methods: Amyloid‐β 1 to 42 peptide (Aβ1–42), total tau (t‐tau), and tau phosphorylated at the threonine 181 were measured in (1) cerebrospinal fluid (CSF) samples obtained during baseline evaluation of 100 mild AD, 196 mild cognitive impairment, and 114 elderly cognitively normal (NC) subjects in ADNI; and (2) independent 56 autopsy‐confirmed AD cases and 52 age‐matched elderly NCs using a multiplex immunoassay. Detection of an AD CSF profile for t‐tau and Aβ1–42 in ADNI subjects was achieved using receiver operating characteristic cut points and logistic regression models derived from the autopsy‐confirmed CSF data. Results: CSF Aβ1–42 was the most sensitive biomarker for AD in the autopsy cohort of CSF samples: receiver operating characteristic area under the curve of 0.913 and sensitivity for AD detection of 96.4%. In the ADNI cohort, a logistic regression model for Aβ1–42, t‐tau, and APOε4 allele count provided the best assessment delineation of mild AD. An AD‐like baseline CSF profile for t‐tau/Aβ1–42 was detected in 33 of 37 ADNI mild cognitive impairment subjects who converted to probable AD during the first year of the study. Interpretation: The CSF biomarker signature of AD defined by Aβ1–42 and t‐tau in the autopsy‐confirmed AD cohort and confirmed in the cohort followed in ADNI for 12 months detects mild AD in a large, multisite, prospective clinical investigation, and this signature appears to predict conversion from mild cognitive impairment to AD. Ann Neurol 2009</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Leslie M. Shaw PhD</name><affiliations><json:string>Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</json:string></affiliations></json:item><json:item><name>Hugo Vanderstichele PhD</name><affiliations><json:string>Department of Diagnostic Development, Innogenetics NV, Gent, Belgium</json:string></affiliations></json:item><json:item><name>Malgorzata Knapik‐Czajka PhD</name><affiliations><json:string>Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</json:string></affiliations></json:item><json:item><name>Christopher M. Clark MD</name><affiliations><json:string>Department of Neurology, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</json:string></affiliations></json:item><json:item><name>Paul S. Aisen MD</name><affiliations><json:string>University of California San Diego, San Diego, CA</json:string></affiliations></json:item><json:item><name>Ronald C. Petersen MD</name><affiliations><json:string>Mayo Clinic College of Medicine, Rochester, MN</json:string></affiliations></json:item><json:item><name>Kaj Blennow MD, PhD</name><affiliations><json:string>Department of Psychiatry and Neurochemistry, Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Göteborg University, Mölndal, Sweden</json:string></affiliations></json:item><json:item><name>Holly Soares PhD</name><affiliations><json:string>Pfizer Global Research and Development, Groton, CT</json:string></affiliations></json:item><json:item><name>Adam Simon PhD</name><affiliations><json:string>Merck Research Laboratories, West Point, PA</json:string></affiliations></json:item><json:item><name>Piotr Lewczuk MD, PhD</name><affiliations><json:string>Department of Psychiatry and Psychotherapy, University of Erlangen‐Nuremberg, Erlangen, Germany</json:string></affiliations></json:item><json:item><name>Robert Dean MD</name><affiliations><json:string>Eli Lilly & Company, Indianapolis, IN</json:string></affiliations></json:item><json:item><name>Eric Siemers MD</name><affiliations><json:string>Eli Lilly & Company, Indianapolis, IN</json:string></affiliations></json:item><json:item><name>William Potter MD</name><affiliations><json:string>Merck Research Laboratories, West Point, PA</json:string></affiliations></json:item><json:item><name>Virginia M.‐Y. Lee PhD</name><affiliations><json:string>Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</json:string></affiliations></json:item><json:item><name>John Q. Trojanowski MD, PhD</name><affiliations><json:string>Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</json:string></affiliations></json:item></author><articleId><json:string>ANA21610</json:string></articleId><language><json:string>eng</json:string></language><abstract>Objective: Develop a cerebrospinal fluid biomarker signature for mild Alzheimer's disease (AD) in Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects. Methods: Amyloid‐β 1 to 42 peptide (Aβ1–42), total tau (t‐tau), and tau phosphorylated at the threonine 181 were measured in (1) cerebrospinal fluid (CSF) samples obtained during baseline evaluation of 100 mild AD, 196 mild cognitive impairment, and 114 elderly cognitively normal (NC) subjects in ADNI; and (2) independent 56 autopsy‐confirmed AD cases and 52 age‐matched elderly NCs using a multiplex immunoassay. Detection of an AD CSF profile for t‐tau and Aβ1–42 in ADNI subjects was achieved using receiver operating characteristic cut points and logistic regression models derived from the autopsy‐confirmed CSF data. Results: CSF Aβ1–42 was the most sensitive biomarker for AD in the autopsy cohort of CSF samples: receiver operating characteristic area under the curve of 0.913 and sensitivity for AD detection of 96.4%. In the ADNI cohort, a logistic regression model for Aβ1–42, t‐tau, and APOε4 allele count provided the best assessment delineation of mild AD. An AD‐like baseline CSF profile for t‐tau/Aβ1–42 was detected in 33 of 37 ADNI mild cognitive impairment subjects who converted to probable AD during the first year of the study. Interpretation: The CSF biomarker signature of AD defined by Aβ1–42 and t‐tau in the autopsy‐confirmed AD cohort and confirmed in the cohort followed in ADNI for 12 months detects mild AD in a large, multisite, prospective clinical investigation, and this signature appears to predict conversion from mild cognitive impairment to AD. Ann Neurol 2009</abstract><qualityIndicators><score>8</score><pdfVersion>1.3</pdfVersion><pdfPageSize>594 x 783 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>0</keywordCount><abstractCharCount>1660</abstractCharCount><pdfWordCount>6423</pdfWordCount><pdfCharCount>40017</pdfCharCount><pdfPageCount>11</pdfPageCount><abstractWordCount>252</abstractWordCount></qualityIndicators><title>Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects</title><corporate><json:item><name>Alzheimer's Disease Neuroimaging Initiative</name></json:item></corporate><genre><json:string>article</json:string></genre><host><volume>65</volume><publisherId><json:string>ANA</json:string></publisherId><pages><total>12</total><last>413</last><first>403</first></pages><issn><json:string>0364-5134</json:string></issn><issue>4</issue><subject><json:item><value>Original Article</value></json:item></subject><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1531-8249</json:string></eissn><title>Annals of Neurology</title><doi><json:string>10.1002/(ISSN)1531-8249</json:string></doi></host><publicationDate>2009</publicationDate><copyrightDate>2009</copyrightDate><doi><json:string>10.1002/ana.21610</json:string></doi><id>FF9CA806BB069C2D45DF06E71E5969BD9215758B</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/FF9CA806BB069C2D45DF06E71E5969BD9215758B/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/FF9CA806BB069C2D45DF06E71E5969BD9215758B/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/FF9CA806BB069C2D45DF06E71E5969BD9215758B/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>WILEY</p></availability><date>2009</date></publicationStmt><notesStmt><note type="content">*Potential conflict of interest: Nothing to report.</note><note>NIH (National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering) - No. AG024904; No. AG10124;</note><note>Foundation for the National Institutes of Health</note><note>Pfizer</note><note>Wyeth Research</note><note>Bristol‐Myers Squibb</note><note>Eli Lilly & Company</note><note>GlaxoSmithKline</note><note>Merck & Company</note><note>AstraZeneca AB</note><note>Novartis Pharmaceuticals Corporation</note><note>Alzheimer's Association</note><note>Eisai Global Clinical Development</note><note>Elan Corporation plc</note><note>Forest Laboratories</note><note>Institute for the Study of Aging</note><note>U.S. Food and Drug Administration</note><note>William Maul Measy‐Truman G. Schnabel Jr MD Professorship of Geriatric Medicine and Gerontology</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects</title><author><orgName>Alzheimer's Disease Neuroimaging Initiative</orgName></author><author><persName><forename type="first">Leslie M.</forename><surname>Shaw</surname></persName><roleName type="degree">PhD</roleName><note type="correspondence"><p>Correspondence: Department of Pathology and Laboratory Medicine, 7 Founders, University of Pennsylvania Medical Center, 3400 Spruce Street, Philadelphia, PA 19104</p></note><affiliation>Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</affiliation></author><author><persName><forename type="first">Hugo</forename><surname>Vanderstichele</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Diagnostic Development, Innogenetics NV, Gent, Belgium</affiliation></author><author><persName><forename type="first">Malgorzata</forename><surname>Knapik‐Czajka</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</affiliation></author><author><persName><forename type="first">Christopher M.</forename><surname>Clark</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</affiliation></author><author><persName><forename type="first">Paul S.</forename><surname>Aisen</surname></persName><roleName type="degree">MD</roleName><affiliation>University of California San Diego, San Diego, CA</affiliation></author><author><persName><forename type="first">Ronald C.</forename><surname>Petersen</surname></persName><roleName type="degree">MD</roleName><affiliation>Mayo Clinic College of Medicine, Rochester, MN</affiliation></author><author><persName><forename type="first">Kaj</forename><surname>Blennow</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Psychiatry and Neurochemistry, Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Göteborg University, Mölndal, Sweden</affiliation></author><author><persName><forename type="first">Holly</forename><surname>Soares</surname></persName><roleName type="degree">PhD</roleName><affiliation>Pfizer Global Research and Development, Groton, CT</affiliation></author><author><persName><forename type="first">Adam</forename><surname>Simon</surname></persName><roleName type="degree">PhD</roleName><affiliation>Merck Research Laboratories, West Point, PA</affiliation></author><author><persName><forename type="first">Piotr</forename><surname>Lewczuk</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Psychiatry and Psychotherapy, University of Erlangen‐Nuremberg, Erlangen, Germany</affiliation></author><author><persName><forename type="first">Robert</forename><surname>Dean</surname></persName><roleName type="degree">MD</roleName><affiliation>Eli Lilly & Company, Indianapolis, IN</affiliation></author><author><persName><forename type="first">Eric</forename><surname>Siemers</surname></persName><roleName type="degree">MD</roleName><affiliation>Eli Lilly & Company, Indianapolis, IN</affiliation></author><author><persName><forename type="first">William</forename><surname>Potter</surname></persName><roleName type="degree">MD</roleName><affiliation>Merck Research Laboratories, West Point, PA</affiliation></author><author><persName><forename type="first">Virginia M.‐Y.</forename><surname>Lee</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</affiliation></author><author><persName><forename type="first">John Q.</forename><surname>Trojanowski</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</affiliation></author></analytic><monogr><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="pISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><idno type="DOI">10.1002/(ISSN)1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2009-04"></date><biblScope unit="volume">65</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="403">403</biblScope><biblScope unit="page" to="413">413</biblScope></imprint></monogr><idno type="istex">FF9CA806BB069C2D45DF06E71E5969BD9215758B</idno><idno type="DOI">10.1002/ana.21610</idno><idno type="ArticleID">ANA21610</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2009</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Objective: Develop a cerebrospinal fluid biomarker signature for mild Alzheimer's disease (AD) in Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects. Methods: Amyloid‐β 1 to 42 peptide (Aβ1–42), total tau (t‐tau), and tau phosphorylated at the threonine 181 were measured in (1) cerebrospinal fluid (CSF) samples obtained during baseline evaluation of 100 mild AD, 196 mild cognitive impairment, and 114 elderly cognitively normal (NC) subjects in ADNI; and (2) independent 56 autopsy‐confirmed AD cases and 52 age‐matched elderly NCs using a multiplex immunoassay. Detection of an AD CSF profile for t‐tau and Aβ1–42 in ADNI subjects was achieved using receiver operating characteristic cut points and logistic regression models derived from the autopsy‐confirmed CSF data. Results: CSF Aβ1–42 was the most sensitive biomarker for AD in the autopsy cohort of CSF samples: receiver operating characteristic area under the curve of 0.913 and sensitivity for AD detection of 96.4%. In the ADNI cohort, a logistic regression model for Aβ1–42, t‐tau, and APOε4 allele count provided the best assessment delineation of mild AD. An AD‐like baseline CSF profile for t‐tau/Aβ1–42 was detected in 33 of 37 ADNI mild cognitive impairment subjects who converted to probable AD during the first year of the study. Interpretation: The CSF biomarker signature of AD defined by Aβ1–42 and t‐tau in the autopsy‐confirmed AD cohort and confirmed in the cohort followed in ADNI for 12 months detects mild AD in a large, multisite, prospective clinical investigation, and this signature appears to predict conversion from mild cognitive impairment to AD. Ann Neurol 2009</p></abstract><textClass><keywords scheme="Journal Subject"><list><head>article category</head><item><term>Original Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2008-09-18">Received</change><change when="2008-11-14">Registration</change><change when="2009-04">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/FF9CA806BB069C2D45DF06E71E5969BD9215758B/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1531-8249</doi><issn type="print">0364-5134</issn><issn type="electronic">1531-8249</issn><idGroup><id type="product" value="ANA"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="ANNALS OF NEUROLOGY">Annals of Neurology</title><title type="short">Ann Neurol.</title></titleGroup></publicationMeta><publicationMeta level="part" position="40"><doi origin="wiley" registered="yes">10.1002/ana.v65:4</doi><numberingGroup><numbering type="journalVolume" number="65">65</numbering><numbering type="journalIssue">4</numbering></numberingGroup><coverDate startDate="2009-04">April 2009</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="110" status="forIssue"><doi origin="wiley" registered="yes">10.1002/ana.21610</doi><idGroup><id type="unit" value="ANA21610"></id></idGroup><countGroup><count type="pageTotal" number="12"></count></countGroup><titleGroup><title type="articleCategory">Original Article</title><title type="tocHeading1">Original Articles</title></titleGroup><copyright ownership="thirdParty">Copyright © 2009 American Neurological Association</copyright><eventGroup><event type="manuscriptReceived" date="2008-09-18"></event><event type="manuscriptRevised" date="2008-11-04"></event><event type="manuscriptAccepted" date="2008-11-14"></event><event type="firstOnline" date="2009-03-18"></event><event type="publishedOnlineFinalForm" date="2009-04-27"></event><event type="publishedOnlineAcceptedOrEarlyUnpaginated" date="2009-03-18"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.4.7 mode:FullText source:FullText result:FullText" date="2011-02-24"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-03"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-14"></event></eventGroup><numberingGroup><numbering type="pageFirst">403</numbering><numbering type="pageLast">413</numbering></numberingGroup><correspondenceTo>Department of Pathology and Laboratory Medicine, 7 Founders, University of Pennsylvania Medical Center, 3400 Spruce Street, Philadelphia, PA 19104</correspondenceTo><objectNameGroup><objectName elementName="appendix">Appendix</objectName></objectNameGroup><linkGroup><link type="toTypesetVersion" href="file:ANA.ANA21610.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="4"></count><count type="tableTotal" number="5"></count><count type="referenceTotal" number="29"></count><count type="wordTotal" number="7350"></count></countGroup><titleGroup><title type="main" xml:lang="en">Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects<link href="#fn1"></link></title><title type="short" xml:lang="en">ADNI CSF Biomarker Profile</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>Leslie M.</givenNames><familyName>Shaw</familyName><degrees>PhD</degrees></personName><contactDetails><email>shawlmj@mail.med.upenn.edu</email></contactDetails></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Hugo</givenNames><familyName>Vanderstichele</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Malgorzata</givenNames><familyName>Knapik‐Czajka</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Christopher M.</givenNames><familyName>Clark</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Paul S.</givenNames><familyName>Aisen</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af5"><personName><givenNames>Ronald C.</givenNames><familyName>Petersen</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af6"><personName><givenNames>Kaj</givenNames><familyName>Blennow</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af7"><personName><givenNames>Holly</givenNames><familyName>Soares</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af8"><personName><givenNames>Adam</givenNames><familyName>Simon</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au10" creatorRole="author" affiliationRef="#af9"><personName><givenNames>Piotr</givenNames><familyName>Lewczuk</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au11" creatorRole="author" affiliationRef="#af10"><personName><givenNames>Robert</givenNames><familyName>Dean</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au12" creatorRole="author" affiliationRef="#af10"><personName><givenNames>Eric</givenNames><familyName>Siemers</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au13" creatorRole="author" affiliationRef="#af8"><personName><givenNames>William</givenNames><familyName>Potter</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au14" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Virginia M.‐Y.</givenNames><familyName>Lee</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au15" creatorRole="author" affiliationRef="#af1"><personName><givenNames>John Q.</givenNames><familyName>Trojanowski</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au16" creatorRole="author"><groupName>Alzheimer's Disease Neuroimaging Initiative</groupName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="US" type="organization"><unparsedAffiliation>Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="BE" type="organization"><unparsedAffiliation>Department of Diagnostic Development, Innogenetics NV, Gent, Belgium</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="US" type="organization"><unparsedAffiliation>University of California San Diego, San Diego, CA</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="US" type="organization"><unparsedAffiliation>Mayo Clinic College of Medicine, Rochester, MN</unparsedAffiliation></affiliation><affiliation xml:id="af6" countryCode="SE" type="organization"><unparsedAffiliation>Department of Psychiatry and Neurochemistry, Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Göteborg University, Mölndal, Sweden</unparsedAffiliation></affiliation><affiliation xml:id="af7" countryCode="US" type="organization"><unparsedAffiliation>Pfizer Global Research and Development, Groton, CT</unparsedAffiliation></affiliation><affiliation xml:id="af8" countryCode="US" type="organization"><unparsedAffiliation>Merck Research Laboratories, West Point, PA</unparsedAffiliation></affiliation><affiliation xml:id="af9" countryCode="DE" type="organization"><unparsedAffiliation>Department of Psychiatry and Psychotherapy, University of Erlangen‐Nuremberg, Erlangen, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af10" countryCode="US" type="organization"><unparsedAffiliation>Eli Lilly & Company, Indianapolis, IN</unparsedAffiliation></affiliation></affiliationGroup><fundingInfo><fundingAgency>NIH (National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering)</fundingAgency><fundingNumber>AG024904</fundingNumber><fundingNumber>AG10124</fundingNumber></fundingInfo><fundingInfo><fundingAgency>Foundation for the National Institutes of Health</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Pfizer</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Wyeth Research</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Bristol‐Myers Squibb</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Eli Lilly & Company</fundingAgency></fundingInfo><fundingInfo><fundingAgency>GlaxoSmithKline</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Merck & Company</fundingAgency></fundingInfo><fundingInfo><fundingAgency>AstraZeneca AB</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Novartis Pharmaceuticals Corporation</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Alzheimer's Association</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Eisai Global Clinical Development</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Elan Corporation plc</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Forest Laboratories</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Institute for the Study of Aging</fundingAgency></fundingInfo><fundingInfo><fundingAgency>U.S. Food and Drug Administration</fundingAgency></fundingInfo><fundingInfo><fundingAgency>William Maul Measy‐Truman G. Schnabel Jr MD Professorship of Geriatric Medicine and Gerontology</fundingAgency></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><section xml:id="abs1-1"><title type="main">Objective</title><p>Develop a cerebrospinal fluid biomarker signature for mild Alzheimer's disease (AD) in Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects.</p></section><section xml:id="abs1-2"><title type="main">Methods</title><p>Amyloid‐β 1 to 42 peptide (Aβ<sub>1–42</sub>), total tau (t‐tau), and tau phosphorylated at the threonine 181 were measured in (1) cerebrospinal fluid (CSF) samples obtained during baseline evaluation of 100 mild AD, 196 mild cognitive impairment, and 114 elderly cognitively normal (NC) subjects in ADNI; and (2) independent 56 autopsy‐confirmed AD cases and 52 age‐matched elderly NCs using a multiplex immunoassay. Detection of an AD CSF profile for t‐tau and Aβ<sub>1–42</sub> in ADNI subjects was achieved using receiver operating characteristic cut points and logistic regression models derived from the autopsy‐confirmed CSF data.</p></section><section xml:id="abs1-3"><title type="main">Results</title><p>CSF Aβ<sub>1–42</sub> was the most sensitive biomarker for AD in the autopsy cohort of CSF samples: receiver operating characteristic area under the curve of 0.913 and sensitivity for AD detection of 96.4%. In the ADNI cohort, a logistic regression model for Aβ<sub>1–42</sub>, t‐tau, and <i>APO</i>ε<i>4</i> allele count provided the best assessment delineation of mild AD. An AD‐like baseline CSF profile for t‐tau/Aβ<sub>1–42</sub> was detected in 33 of 37 ADNI mild cognitive impairment subjects who converted to probable AD during the first year of the study.</p></section><section xml:id="abs1-4"><title type="main">Interpretation</title><p>The CSF biomarker signature of AD defined by Aβ<sub>1–42</sub> and t‐tau in the autopsy‐confirmed AD cohort and confirmed in the cohort followed in ADNI for 12 months detects mild AD in a large, multisite, prospective clinical investigation, and this signature appears to predict conversion from mild cognitive impairment to AD. Ann Neurol 2009</p></section></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>Potential conflict of interest: Nothing to report.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>ADNI CSF Biomarker Profile</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects</title></titleInfo><name type="personal"><namePart type="given">Leslie M.</namePart><namePart type="family">Shaw</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</affiliation><description>Correspondence: Department of Pathology and Laboratory Medicine, 7 Founders, University of Pennsylvania Medical Center, 3400 Spruce Street, Philadelphia, PA 19104</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hugo</namePart><namePart type="family">Vanderstichele</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Diagnostic Development, Innogenetics NV, Gent, Belgium</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Malgorzata</namePart><namePart type="family">Knapik‐Czajka</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christopher M.</namePart><namePart type="family">Clark</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Paul S.</namePart><namePart type="family">Aisen</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>University of California San Diego, San Diego, CA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ronald C.</namePart><namePart type="family">Petersen</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Mayo Clinic College of Medicine, Rochester, MN</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kaj</namePart><namePart type="family">Blennow</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Psychiatry and Neurochemistry, Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Göteborg University, Mölndal, Sweden</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Holly</namePart><namePart type="family">Soares</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Pfizer Global Research and Development, Groton, CT</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Adam</namePart><namePart type="family">Simon</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Merck Research Laboratories, West Point, PA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Piotr</namePart><namePart type="family">Lewczuk</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Psychiatry and Psychotherapy, University of Erlangen‐Nuremberg, Erlangen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Robert</namePart><namePart type="family">Dean</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Eli Lilly & Company, Indianapolis, IN</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Eric</namePart><namePart type="family">Siemers</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Eli Lilly & Company, Indianapolis, IN</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">William</namePart><namePart type="family">Potter</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Merck Research Laboratories, West Point, PA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Virginia M.‐Y.</namePart><namePart type="family">Lee</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">John Q.</namePart><namePart type="family">Trojanowski</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="corporate"><namePart>Alzheimer's Disease Neuroimaging Initiative</namePart><description>Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PADepartment of Diagnostic Development, Innogenetics NV, Gent, BelgiumDepartment of Neurology, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PAUniversity of California San Diego, San Diego, CAMayo Clinic College of Medicine, Rochester, MNDepartment of Psychiatry and Neurochemistry, Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Göteborg University, Mölndal, SwedenPfizer Global Research and Development, Groton, CTMerck Research Laboratories, West Point, PADepartment of Psychiatry and Psychotherapy, University of Erlangen‐Nuremberg, Erlangen, GermanyEli Lilly & Company, Indianapolis, IN</description></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2009-04</dateIssued><dateCaptured encoding="w3cdtf">2008-09-18</dateCaptured><dateValid encoding="w3cdtf">2008-11-14</dateValid><copyrightDate encoding="w3cdtf">2009</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">4</extent><extent unit="tables">5</extent><extent unit="references">29</extent><extent unit="words">7350</extent></physicalDescription><abstract lang="en">Objective: Develop a cerebrospinal fluid biomarker signature for mild Alzheimer's disease (AD) in Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects. Methods: Amyloid‐β 1 to 42 peptide (Aβ1–42), total tau (t‐tau), and tau phosphorylated at the threonine 181 were measured in (1) cerebrospinal fluid (CSF) samples obtained during baseline evaluation of 100 mild AD, 196 mild cognitive impairment, and 114 elderly cognitively normal (NC) subjects in ADNI; and (2) independent 56 autopsy‐confirmed AD cases and 52 age‐matched elderly NCs using a multiplex immunoassay. Detection of an AD CSF profile for t‐tau and Aβ1–42 in ADNI subjects was achieved using receiver operating characteristic cut points and logistic regression models derived from the autopsy‐confirmed CSF data. Results: CSF Aβ1–42 was the most sensitive biomarker for AD in the autopsy cohort of CSF samples: receiver operating characteristic area under the curve of 0.913 and sensitivity for AD detection of 96.4%. In the ADNI cohort, a logistic regression model for Aβ1–42, t‐tau, and APOε4 allele count provided the best assessment delineation of mild AD. An AD‐like baseline CSF profile for t‐tau/Aβ1–42 was detected in 33 of 37 ADNI mild cognitive impairment subjects who converted to probable AD during the first year of the study. Interpretation: The CSF biomarker signature of AD defined by Aβ1–42 and t‐tau in the autopsy‐confirmed AD cohort and confirmed in the cohort followed in ADNI for 12 months detects mild AD in a large, multisite, prospective clinical investigation, and this signature appears to predict conversion from mild cognitive impairment to AD. Ann Neurol 2009</abstract><note type="content">*Potential conflict of interest: Nothing to report.</note><note type="funding">NIH (National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering) - No. AG024904; No. AG10124; </note><note type="funding">Foundation for the National Institutes of Health</note><note type="funding">Pfizer</note><note type="funding">Wyeth Research</note><note type="funding">Bristol‐Myers Squibb</note><note type="funding">Eli Lilly & Company</note><note type="funding">GlaxoSmithKline</note><note type="funding">Merck & Company</note><note type="funding">AstraZeneca AB</note><note type="funding">Novartis Pharmaceuticals Corporation</note><note type="funding">Alzheimer's Association</note><note type="funding">Eisai Global Clinical Development</note><note type="funding">Elan Corporation plc</note><note type="funding">Forest Laboratories</note><note type="funding">Institute for the Study of Aging</note><note type="funding">U.S. Food and Drug Administration</note><note type="funding">William Maul Measy‐Truman G. Schnabel Jr MD Professorship of Geriatric Medicine and Gerontology</note><relatedItem type="host"><titleInfo><title>Annals of Neurology</title></titleInfo><titleInfo type="abbreviated"><title>Ann Neurol.</title></titleInfo><genre type="Journal">journal</genre><subject><genre>article category</genre><topic>Original Article</topic></subject><identifier type="ISSN">0364-5134</identifier><identifier type="eISSN">1531-8249</identifier><identifier type="DOI">10.1002/(ISSN)1531-8249</identifier><identifier type="PublisherID">ANA</identifier><part><date>2009</date><detail type="volume"><caption>vol.</caption><number>65</number></detail><detail type="issue"><caption>no.</caption><number>4</number></detail><extent unit="pages"><start>403</start><end>413</end><total>12</total></extent></part></relatedItem><identifier type="istex">FF9CA806BB069C2D45DF06E71E5969BD9215758B</identifier><identifier type="DOI">10.1002/ana.21610</identifier><identifier type="ArticleID">ANA21610</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2009 American Neurological Association</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002E47 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd -nk 002E47 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Corpus
|type= RBID
|clé= ISTEX:FF9CA806BB069C2D45DF06E71E5969BD9215758B
|texte= Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects
}}
| This area was generated with Dilib version V0.6.23. |  |