Alzheimer’s disease cerebrospinal fluid biomarker in cognitively normal subjects
Identifieur interne : 000040 ( Pmc/Curation ); précédent : 000039; suivant : 000041Alzheimer’s disease cerebrospinal fluid biomarker in cognitively normal subjects
Auteurs : Jon B. Toledo [États-Unis] ; Henrik Zetterberg [Suède, Royaume-Uni] ; Argonde C. Van Harten [Pays-Bas] ; Lidia Glodzik [États-Unis] ; Pablo Martinez-Lage [Espagne] ; Luisella Bocchio-Chiavetto [Italie] ; Lorena Rami [Espagne] ; Oskar Hansson [Suède] ; Reisa Sperling [Suède] ; Sebastiaan Engelborghs [Belgique] ; Ricardo S. Osorio [États-Unis] ; Hugo Vanderstichele [Belgique] ; Manu Vandijck [Belgique] ; Harald Hampel [France] ; Stefan Teipl [Allemagne] ; Abhay Moghekar [États-Unis] ; Marilyn Albert [États-Unis] ; William T. Hu [États-Unis] ; Jose A. Monge Argilés [Espagne] ; Ana Gorostidi [Espagne] ; Charlotte E. Teunissen [Pays-Bas] ; Peter P. De Deyn [Belgique] ; Bradley T. Hyman [États-Unis] ; Jose L. Molinuevo [Espagne] ; Giovanni B. Frisoni [Italie, Suisse] ; Gurutz Linazasoro [Espagne] ; Mony J. De Leon [États-Unis] ; Wiesje M. Van Der Flier [Pays-Bas, États-Unis] ; Philip Scheltens [Pays-Bas] ; Kaj Blennow [Suède, États-Unis] ; Leslie M. Shaw [États-Unis] ; John Q. Trojanowski [États-Unis]Source :
- Brain [ 0006-8950 ] ; 2015.
Abstract
In a large multicentre study, Toledo et al. examine core Alzheimer’s disease CSF biomarkers in 1233 cognitively normal subjects aged 40–85 years. Alzheimer disease-like changes in Aβ1-42 are seen as early as middle age, while APOE genotype strongly modifies age-related effects on both Aβ1–42 and phosphorylated/total tau.
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DOI: 10.1093/brain/awv199
PubMed: 26220940
PubMed Central: 4643624
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Toledo</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF1">1 Department of Pathology and Laboratory Medicine, Institute on Aging, Centre for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>1 Department of Pathology and Laboratory Medicine, Institute on Aging, Centre for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA</wicri:regionArea></affiliation></author><author><name sortKey="Zetterberg, Henrik" sort="Zetterberg, Henrik" uniqKey="Zetterberg H" first="Henrik" last="Zetterberg">Henrik Zetterberg</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF2">2 Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>2 Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="awv199-AFF3">3 UCL Institute of Neurology, Department of Molecular Neuroscience, Queen Square, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>3 UCL Institute of Neurology, Department of Molecular Neuroscience, Queen Square, London</wicri:regionArea></affiliation></author><author><name sortKey="Van Harten, Argonde C" sort="Van Harten, Argonde C" uniqKey="Van Harten A" first="Argonde C." last="Van Harten">Argonde C. 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Osorio</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF5">5 Centre for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>5 Centre for Brain Health, Department of Psychiatry, New York University School of Medicine, New York</wicri:regionArea></affiliation></author><author><name sortKey="Vanderstichele, Hugo" sort="Vanderstichele, Hugo" uniqKey="Vanderstichele H" first="Hugo" last="Vanderstichele">Hugo Vanderstichele</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF15">15 ADx NeuroSciences, Technologiepark 4, Gent, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>15 ADx NeuroSciences, Technologiepark 4, Gent</wicri:regionArea></affiliation></author><author><name sortKey="Vandijck, Manu" sort="Vandijck, Manu" uniqKey="Vandijck M" first="Manu" last="Vandijck">Manu Vandijck</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF16">16 Fujirebio Europe nv, Technologiepark 6, Gent, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>16 Fujirebio Europe nv, Technologiepark 6, Gent</wicri:regionArea></affiliation></author><author><name sortKey="Hampel, Harald" sort="Hampel, Harald" uniqKey="Hampel H" first="Harald" last="Hampel">Harald Hampel</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF17">17 AXA Research Fund and UPMC, Université Pierre et Marie Curie, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>17 AXA Research Fund and UPMC, Université Pierre et Marie Curie, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="awv199-AFF18">18 Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, Institut de la Mémoire et de la Maladie d’Alzheimer (IM2A) & Institut du Cerveau et de la Moelle épinière (ICM), Département de Neurologie, Hôpital de la Pitié-Salpétrière, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>18 Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, Institut de la Mémoire et de la Maladie d’Alzheimer (IM2A) & Institut du Cerveau et de la Moelle épinière (ICM), Département de Neurologie, Hôpital de la Pitié-Salpétrière, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Teipl, Stefan" sort="Teipl, Stefan" uniqKey="Teipl S" first="Stefan" last="Teipl">Stefan Teipl</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF19">19 Department of Psychosomatic Medicine, University Medicine Rostock, Rostock, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>19 Department of Psychosomatic Medicine, University Medicine Rostock, Rostock</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="awv199-AFF20">20 DZNE, German Centre for Neurodegenerative Diseases, Rostock, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>20 DZNE, German Centre for Neurodegenerative Diseases, Rostock</wicri:regionArea></affiliation></author><author><name sortKey="Moghekar, Abhay" sort="Moghekar, Abhay" uniqKey="Moghekar A" first="Abhay" last="Moghekar">Abhay Moghekar</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF21">21 Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>21 Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea></affiliation></author><author><name sortKey="Albert, Marilyn" sort="Albert, Marilyn" uniqKey="Albert M" first="Marilyn" last="Albert">Marilyn Albert</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF21">21 Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>21 Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea></affiliation></author><author><name sortKey="Hu, William T" sort="Hu, William T" uniqKey="Hu W" first="William T." last="Hu">William T. Hu</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF22">22 Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>22 Department of Neurology, Emory University School of Medicine, Atlanta, GA</wicri:regionArea></affiliation></author><author><name sortKey="Monge Argiles, Jose A" sort="Monge Argiles, Jose A" uniqKey="Monge Argiles J" first="Jose A." last="Monge Argilés">Jose A. Monge Argilés</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF23">23 Department of Neurology, University General Hospital of Alicante, Alicante, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>23 Department of Neurology, University General Hospital of Alicante, Alicante</wicri:regionArea></affiliation></author><author><name sortKey="Gorostidi, Ana" sort="Gorostidi, Ana" uniqKey="Gorostidi A" first="Ana" last="Gorostidi">Ana Gorostidi</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF24">24 Neuroscience Unit, Biodonostia Research Institute, San Sebastian, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>24 Neuroscience Unit, Biodonostia Research Institute, San Sebastian</wicri:regionArea></affiliation></author><author><name sortKey="Teunissen, Charlotte E" sort="Teunissen, Charlotte E" uniqKey="Teunissen C" first="Charlotte E." last="Teunissen">Charlotte E. Teunissen</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF25">25 Neurochemistry Lab and Biobank, Dept. of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Centre Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>25 Neurochemistry Lab and Biobank, Dept. of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Centre Amsterdam</wicri:regionArea></affiliation></author><author><name sortKey="De Deyn, Peter P" sort="De Deyn, Peter P" uniqKey="De Deyn P" first="Peter P." last="De Deyn">Peter P. De Deyn</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF13">13 Department of Neurology and Memory Clinic, Hospital Network Antwerp, Middelheim and Hoge Beuken, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>13 Department of Neurology and Memory Clinic, Hospital Network Antwerp, Middelheim and Hoge Beuken</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="awv199-AFF14">14 Reference Centre for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Department of Biomedical Sciences, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>14 Reference Centre for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Department of Biomedical Sciences, Institute Born-Bunge, University of Antwerp, Antwerp</wicri:regionArea></affiliation></author><author><name sortKey="Hyman, Bradley T" sort="Hyman, Bradley T" uniqKey="Hyman B" first="Bradley T." last="Hyman">Bradley T. Hyman</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF12">12 Massachusetts Alzheimer’s Disease Research Centre, Harvard Aging Brain Study, Department of Neurology; Massachusetts General Hospital, Harvard Medical School, Boston, MA,USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>12 Massachusetts Alzheimer’s Disease Research Centre, Harvard Aging Brain Study, Department of Neurology; Massachusetts General Hospital, Harvard Medical School, Boston, MA</wicri:regionArea></affiliation></author><author><name sortKey="Molinuevo, Jose L" sort="Molinuevo, Jose L" uniqKey="Molinuevo J" first="Jose L." last="Molinuevo">Jose L. Molinuevo</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF9">9 Alzheimer’s Disease and Other Cognitive Disorders Unit, Hospital Clinic i Universitari, Barcelona, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>9 Alzheimer’s Disease and Other Cognitive Disorders Unit, Hospital Clinic i Universitari, Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Frisoni, Giovanni B" sort="Frisoni, Giovanni B" uniqKey="Frisoni G" first="Giovanni B." last="Frisoni">Giovanni B. Frisoni</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF7">7 IRCCS Centro San Giovanni di Dio FBF, Brescia, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>7 IRCCS Centro San Giovanni di Dio FBF, Brescia</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="awv199-AFF26">26 University Hospitals and University of Geneva, Geneva, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>26 University Hospitals and University of Geneva, Geneva</wicri:regionArea></affiliation></author><author><name sortKey="Linazasoro, Gurutz" sort="Linazasoro, Gurutz" uniqKey="Linazasoro G" first="Gurutz" last="Linazasoro">Gurutz Linazasoro</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF6">6 Department of Neurology, Centre for Research and Advanced Therapies. Fundación CITA-Alzheimer Fundazioa, Donostia/San Sebastián, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>6 Department of Neurology, Centre for Research and Advanced Therapies. Fundación CITA-Alzheimer Fundazioa, Donostia/San Sebastián</wicri:regionArea></affiliation></author><author><name sortKey="De Leon, Mony J" sort="De Leon, Mony J" uniqKey="De Leon M" first="Mony J." last="De Leon">Mony J. De Leon</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF5">5 Centre for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>5 Centre for Brain Health, Department of Psychiatry, New York University School of Medicine, New York</wicri:regionArea></affiliation></author><author><name sortKey="Van Der Flier, Wiesje M" sort="Van Der Flier, Wiesje M" uniqKey="Van Der Flier W" first="Wiesje M." last="Van Der Flier">Wiesje M. Van Der Flier</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF4">4 Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>4 Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="awv199-AFF27">27 Department of Epidemiology/Biostatistics, VU University Medical Centre, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>27 Department of Epidemiology/Biostatistics, VU University Medical Centre</wicri:regionArea></affiliation></author><author><name sortKey="Scheltens, Philip" sort="Scheltens, Philip" uniqKey="Scheltens P" first="Philip" last="Scheltens">Philip Scheltens</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF4">4 Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>4 Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam</wicri:regionArea></affiliation></author><author><name sortKey="Blennow, Kaj" sort="Blennow, Kaj" uniqKey="Blennow K" first="Kaj" last="Blennow">Kaj Blennow</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF2">2 Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>2 Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="awv199-AFF27">27 Department of Epidemiology/Biostatistics, VU University Medical Centre, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>27 Department of Epidemiology/Biostatistics, VU University Medical Centre</wicri:regionArea></affiliation></author><author><name sortKey="Shaw, Leslie M" sort="Shaw, Leslie M" uniqKey="Shaw L" first="Leslie M." last="Shaw">Leslie M. Shaw</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF1">1 Department of Pathology and Laboratory Medicine, Institute on Aging, Centre for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>1 Department of Pathology and Laboratory Medicine, Institute on Aging, Centre for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA</wicri:regionArea></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 wicri:level="1"><nlm:aff id="awv199-AFF1">1 Department of Pathology and Laboratory Medicine, Institute on Aging, Centre for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>1 Department of Pathology and Laboratory Medicine, Institute on Aging, Centre for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26220940</idno><idno type="pmc">4643624</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643624</idno><idno type="RBID">PMC:4643624</idno><idno type="doi">10.1093/brain/awv199</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000040</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000040</idno><idno type="wicri:Area/Pmc/Curation">000040</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000040</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Alzheimer’s disease cerebrospinal fluid biomarker in cognitively normal subjects</title><author><name sortKey="Toledo, Jon B" sort="Toledo, Jon B" uniqKey="Toledo J" first="Jon B." last="Toledo">Jon B. Toledo</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF1">1 Department of Pathology and Laboratory Medicine, Institute on Aging, Centre for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>1 Department of Pathology and Laboratory Medicine, Institute on Aging, Centre for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA</wicri:regionArea></affiliation></author><author><name sortKey="Zetterberg, Henrik" sort="Zetterberg, Henrik" uniqKey="Zetterberg H" first="Henrik" last="Zetterberg">Henrik Zetterberg</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF2">2 Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>2 Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="awv199-AFF3">3 UCL Institute of Neurology, Department of Molecular Neuroscience, Queen Square, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>3 UCL Institute of Neurology, Department of Molecular Neuroscience, Queen Square, London</wicri:regionArea></affiliation></author><author><name sortKey="Van Harten, Argonde C" sort="Van Harten, Argonde C" uniqKey="Van Harten A" first="Argonde C." last="Van Harten">Argonde C. Van Harten</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF4">4 Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>4 Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam</wicri:regionArea></affiliation></author><author><name sortKey="Glodzik, Lidia" sort="Glodzik, Lidia" uniqKey="Glodzik L" first="Lidia" last="Glodzik">Lidia Glodzik</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF5">5 Centre for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>5 Centre for Brain Health, Department of Psychiatry, New York University School of Medicine, New York</wicri:regionArea></affiliation></author><author><name sortKey="Martinez Lage, Pablo" sort="Martinez Lage, Pablo" uniqKey="Martinez Lage P" first="Pablo" last="Martinez-Lage">Pablo Martinez-Lage</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF6">6 Department of Neurology, Centre for Research and Advanced Therapies. Fundación CITA-Alzheimer Fundazioa, Donostia/San Sebastián, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>6 Department of Neurology, Centre for Research and Advanced Therapies. Fundación CITA-Alzheimer Fundazioa, Donostia/San Sebastián</wicri:regionArea></affiliation></author><author><name sortKey="Bocchio Chiavetto, Luisella" sort="Bocchio Chiavetto, Luisella" uniqKey="Bocchio Chiavetto L" first="Luisella" last="Bocchio-Chiavetto">Luisella Bocchio-Chiavetto</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF7">7 IRCCS Centro San Giovanni di Dio FBF, Brescia, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>7 IRCCS Centro San Giovanni di Dio FBF, Brescia</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="awv199-AFF8">8 Faculty of Psychology, eCampus University, Novedrate (Como), Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>8 Faculty of Psychology, eCampus University, Novedrate (Como)</wicri:regionArea></affiliation></author><author><name sortKey="Rami, Lorena" sort="Rami, Lorena" uniqKey="Rami L" first="Lorena" last="Rami">Lorena Rami</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF9">9 Alzheimer’s Disease and Other Cognitive Disorders Unit, Hospital Clinic i Universitari, Barcelona, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>9 Alzheimer’s Disease and Other Cognitive Disorders Unit, Hospital Clinic i Universitari, Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Hansson, Oskar" sort="Hansson, Oskar" uniqKey="Hansson O" first="Oskar" last="Hansson">Oskar Hansson</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF10">10 Department of Clinical Sciences, Lund University, Lund, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>10 Department of Clinical Sciences, Lund University, Lund</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="awv199-AFF11">11 Memory clinic, Skåne University Hospital, Lund, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>11 Memory clinic, Skåne University Hospital, Lund</wicri:regionArea></affiliation></author><author><name sortKey="Sperling, Reisa" sort="Sperling, Reisa" uniqKey="Sperling R" first="Reisa" last="Sperling">Reisa Sperling</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF11">11 Memory clinic, Skåne University Hospital, Lund, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>11 Memory clinic, Skåne University Hospital, Lund</wicri:regionArea></affiliation></author><author><name sortKey="Engelborghs, Sebastiaan" sort="Engelborghs, Sebastiaan" uniqKey="Engelborghs S" first="Sebastiaan" last="Engelborghs">Sebastiaan Engelborghs</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF13">13 Department of Neurology and Memory Clinic, Hospital Network Antwerp, Middelheim and Hoge Beuken, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>13 Department of Neurology and Memory Clinic, Hospital Network Antwerp, Middelheim and Hoge Beuken</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="awv199-AFF14">14 Reference Centre for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Department of Biomedical Sciences, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>14 Reference Centre for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Department of Biomedical Sciences, Institute Born-Bunge, University of Antwerp, Antwerp</wicri:regionArea></affiliation></author><author><name sortKey="Osorio, Ricardo S" sort="Osorio, Ricardo S" uniqKey="Osorio R" first="Ricardo S." last="Osorio">Ricardo S. Osorio</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF5">5 Centre for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>5 Centre for Brain Health, Department of Psychiatry, New York University School of Medicine, New York</wicri:regionArea></affiliation></author><author><name sortKey="Vanderstichele, Hugo" sort="Vanderstichele, Hugo" uniqKey="Vanderstichele H" first="Hugo" last="Vanderstichele">Hugo Vanderstichele</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF15">15 ADx NeuroSciences, Technologiepark 4, Gent, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>15 ADx NeuroSciences, Technologiepark 4, Gent</wicri:regionArea></affiliation></author><author><name sortKey="Vandijck, Manu" sort="Vandijck, Manu" uniqKey="Vandijck M" first="Manu" last="Vandijck">Manu Vandijck</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF16">16 Fujirebio Europe nv, Technologiepark 6, Gent, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>16 Fujirebio Europe nv, Technologiepark 6, Gent</wicri:regionArea></affiliation></author><author><name sortKey="Hampel, Harald" sort="Hampel, Harald" uniqKey="Hampel H" first="Harald" last="Hampel">Harald Hampel</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF17">17 AXA Research Fund and UPMC, Université Pierre et Marie Curie, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>17 AXA Research Fund and UPMC, Université Pierre et Marie Curie, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="awv199-AFF18">18 Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, Institut de la Mémoire et de la Maladie d’Alzheimer (IM2A) & Institut du Cerveau et de la Moelle épinière (ICM), Département de Neurologie, Hôpital de la Pitié-Salpétrière, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>18 Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, Institut de la Mémoire et de la Maladie d’Alzheimer (IM2A) & Institut du Cerveau et de la Moelle épinière (ICM), Département de Neurologie, Hôpital de la Pitié-Salpétrière, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Teipl, Stefan" sort="Teipl, Stefan" uniqKey="Teipl S" first="Stefan" last="Teipl">Stefan Teipl</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF19">19 Department of Psychosomatic Medicine, University Medicine Rostock, Rostock, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>19 Department of Psychosomatic Medicine, University Medicine Rostock, Rostock</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="awv199-AFF20">20 DZNE, German Centre for Neurodegenerative Diseases, Rostock, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>20 DZNE, German Centre for Neurodegenerative Diseases, Rostock</wicri:regionArea></affiliation></author><author><name sortKey="Moghekar, Abhay" sort="Moghekar, Abhay" uniqKey="Moghekar A" first="Abhay" last="Moghekar">Abhay Moghekar</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF21">21 Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>21 Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea></affiliation></author><author><name sortKey="Albert, Marilyn" sort="Albert, Marilyn" uniqKey="Albert M" first="Marilyn" last="Albert">Marilyn Albert</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF21">21 Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>21 Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea></affiliation></author><author><name sortKey="Hu, William T" sort="Hu, William T" uniqKey="Hu W" first="William T." last="Hu">William T. Hu</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF22">22 Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>22 Department of Neurology, Emory University School of Medicine, Atlanta, GA</wicri:regionArea></affiliation></author><author><name sortKey="Monge Argiles, Jose A" sort="Monge Argiles, Jose A" uniqKey="Monge Argiles J" first="Jose A." last="Monge Argilés">Jose A. Monge Argilés</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF23">23 Department of Neurology, University General Hospital of Alicante, Alicante, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>23 Department of Neurology, University General Hospital of Alicante, Alicante</wicri:regionArea></affiliation></author><author><name sortKey="Gorostidi, Ana" sort="Gorostidi, Ana" uniqKey="Gorostidi A" first="Ana" last="Gorostidi">Ana Gorostidi</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF24">24 Neuroscience Unit, Biodonostia Research Institute, San Sebastian, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>24 Neuroscience Unit, Biodonostia Research Institute, San Sebastian</wicri:regionArea></affiliation></author><author><name sortKey="Teunissen, Charlotte E" sort="Teunissen, Charlotte E" uniqKey="Teunissen C" first="Charlotte E." last="Teunissen">Charlotte E. Teunissen</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF25">25 Neurochemistry Lab and Biobank, Dept. of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Centre Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>25 Neurochemistry Lab and Biobank, Dept. of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Centre Amsterdam</wicri:regionArea></affiliation></author><author><name sortKey="De Deyn, Peter P" sort="De Deyn, Peter P" uniqKey="De Deyn P" first="Peter P." last="De Deyn">Peter P. De Deyn</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF13">13 Department of Neurology and Memory Clinic, Hospital Network Antwerp, Middelheim and Hoge Beuken, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>13 Department of Neurology and Memory Clinic, Hospital Network Antwerp, Middelheim and Hoge Beuken</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="awv199-AFF14">14 Reference Centre for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Department of Biomedical Sciences, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>14 Reference Centre for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Department of Biomedical Sciences, Institute Born-Bunge, University of Antwerp, Antwerp</wicri:regionArea></affiliation></author><author><name sortKey="Hyman, Bradley T" sort="Hyman, Bradley T" uniqKey="Hyman B" first="Bradley T." last="Hyman">Bradley T. Hyman</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF12">12 Massachusetts Alzheimer’s Disease Research Centre, Harvard Aging Brain Study, Department of Neurology; Massachusetts General Hospital, Harvard Medical School, Boston, MA,USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>12 Massachusetts Alzheimer’s Disease Research Centre, Harvard Aging Brain Study, Department of Neurology; Massachusetts General Hospital, Harvard Medical School, Boston, MA</wicri:regionArea></affiliation></author><author><name sortKey="Molinuevo, Jose L" sort="Molinuevo, Jose L" uniqKey="Molinuevo J" first="Jose L." last="Molinuevo">Jose L. Molinuevo</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF9">9 Alzheimer’s Disease and Other Cognitive Disorders Unit, Hospital Clinic i Universitari, Barcelona, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>9 Alzheimer’s Disease and Other Cognitive Disorders Unit, Hospital Clinic i Universitari, Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Frisoni, Giovanni B" sort="Frisoni, Giovanni B" uniqKey="Frisoni G" first="Giovanni B." last="Frisoni">Giovanni B. Frisoni</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF7">7 IRCCS Centro San Giovanni di Dio FBF, Brescia, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>7 IRCCS Centro San Giovanni di Dio FBF, Brescia</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="awv199-AFF26">26 University Hospitals and University of Geneva, Geneva, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>26 University Hospitals and University of Geneva, Geneva</wicri:regionArea></affiliation></author><author><name sortKey="Linazasoro, Gurutz" sort="Linazasoro, Gurutz" uniqKey="Linazasoro G" first="Gurutz" last="Linazasoro">Gurutz Linazasoro</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF6">6 Department of Neurology, Centre for Research and Advanced Therapies. Fundación CITA-Alzheimer Fundazioa, Donostia/San Sebastián, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>6 Department of Neurology, Centre for Research and Advanced Therapies. Fundación CITA-Alzheimer Fundazioa, Donostia/San Sebastián</wicri:regionArea></affiliation></author><author><name sortKey="De Leon, Mony J" sort="De Leon, Mony J" uniqKey="De Leon M" first="Mony J." last="De Leon">Mony J. De Leon</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF5">5 Centre for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>5 Centre for Brain Health, Department of Psychiatry, New York University School of Medicine, New York</wicri:regionArea></affiliation></author><author><name sortKey="Van Der Flier, Wiesje M" sort="Van Der Flier, Wiesje M" uniqKey="Van Der Flier W" first="Wiesje M." last="Van Der Flier">Wiesje M. Van Der Flier</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF4">4 Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>4 Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="awv199-AFF27">27 Department of Epidemiology/Biostatistics, VU University Medical Centre, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>27 Department of Epidemiology/Biostatistics, VU University Medical Centre</wicri:regionArea></affiliation></author><author><name sortKey="Scheltens, Philip" sort="Scheltens, Philip" uniqKey="Scheltens P" first="Philip" last="Scheltens">Philip Scheltens</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF4">4 Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>4 Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam</wicri:regionArea></affiliation></author><author><name sortKey="Blennow, Kaj" sort="Blennow, Kaj" uniqKey="Blennow K" first="Kaj" last="Blennow">Kaj Blennow</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF2">2 Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>2 Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="awv199-AFF27">27 Department of Epidemiology/Biostatistics, VU University Medical Centre, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>27 Department of Epidemiology/Biostatistics, VU University Medical Centre</wicri:regionArea></affiliation></author><author><name sortKey="Shaw, Leslie M" sort="Shaw, Leslie M" uniqKey="Shaw L" first="Leslie M." last="Shaw">Leslie M. Shaw</name><affiliation wicri:level="1"><nlm:aff id="awv199-AFF1">1 Department of Pathology and Laboratory Medicine, Institute on Aging, Centre for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>1 Department of Pathology and Laboratory Medicine, Institute on Aging, Centre for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA</wicri:regionArea></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 wicri:level="1"><nlm:aff id="awv199-AFF1">1 Department of Pathology and Laboratory Medicine, Institute on Aging, Centre for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>1 Department of Pathology and Laboratory Medicine, Institute on Aging, Centre for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA</wicri:regionArea></affiliation></author></analytic><series><title level="j">Brain</title><idno type="ISSN">0006-8950</idno><idno type="eISSN">1460-2156</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>In a large multicentre study, Toledo et al. examine core Alzheimer’s disease CSF biomarkers in 1233 cognitively normal subjects aged 40–85 years. Alzheimer disease-like changes in Aβ1-42 are seen as early as middle age, while APOE genotype strongly modifies age-related effects on both Aβ1–42 and phosphorylated/total tau.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Brain</journal-id><journal-id journal-id-type="iso-abbrev">Brain</journal-id><journal-id journal-id-type="publisher-id">brainj</journal-id><journal-id journal-id-type="hwp">brain</journal-id><journal-title-group><journal-title>Brain</journal-title></journal-title-group><issn pub-type="ppub">0006-8950</issn><issn pub-type="epub">1460-2156</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26220940</article-id><article-id pub-id-type="pmc">4643624</article-id><article-id pub-id-type="doi">10.1093/brain/awv199</article-id><article-id pub-id-type="publisher-id">awv199</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Articles</subject></subj-group><subj-group subj-group-type="hwp-journal-coll"><subject>1010</subject></subj-group><series-title>Editor's Choice</series-title></article-categories><title-group><article-title>Alzheimer’s disease cerebrospinal fluid biomarker in cognitively normal subjects</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Toledo</surname><given-names>Jon B.</given-names></name><xref ref-type="aff" rid="awv199-AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zetterberg</surname><given-names>Henrik</given-names></name><xref ref-type="aff" rid="awv199-AFF2"><sup>2</sup></xref><xref ref-type="aff" rid="awv199-AFF3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>van Harten</surname><given-names>Argonde C.</given-names></name><xref ref-type="aff" rid="awv199-AFF4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Glodzik</surname><given-names>Lidia</given-names></name><xref ref-type="aff" rid="awv199-AFF5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Martinez-Lage</surname><given-names>Pablo</given-names></name><xref ref-type="aff" rid="awv199-AFF6"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bocchio-Chiavetto</surname><given-names>Luisella</given-names></name><xref ref-type="aff" rid="awv199-AFF7"><sup>7</sup></xref><xref ref-type="aff" rid="awv199-AFF8"><sup>8</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rami</surname><given-names>Lorena</given-names></name><xref ref-type="aff" rid="awv199-AFF9"><sup>9</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hansson</surname><given-names>Oskar</given-names></name><xref ref-type="aff" rid="awv199-AFF10"><sup>10</sup></xref><xref ref-type="aff" rid="awv199-AFF11"><sup>11</sup></xref></contrib><contrib contrib-type="author"><name><surname>Sperling</surname><given-names>Reisa</given-names></name><xref ref-type="aff" rid="awv199-AFF11"><sup>12</sup></xref></contrib><contrib contrib-type="author"><name><surname>Engelborghs</surname><given-names>Sebastiaan</given-names></name><xref ref-type="aff" rid="awv199-AFF13"><sup>13</sup></xref><xref ref-type="aff" rid="awv199-AFF14"><sup>14</sup></xref></contrib><contrib contrib-type="author"><name><surname>Osorio</surname><given-names>Ricardo S.</given-names></name><xref ref-type="aff" rid="awv199-AFF5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Vanderstichele</surname><given-names>Hugo</given-names></name><xref ref-type="aff" rid="awv199-AFF15"><sup>15</sup></xref></contrib><contrib contrib-type="author"><name><surname>Vandijck</surname><given-names>Manu</given-names></name><xref ref-type="aff" rid="awv199-AFF16"><sup>16</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hampel</surname><given-names>Harald</given-names></name><xref ref-type="aff" rid="awv199-AFF17"><sup>17</sup></xref><xref ref-type="aff" rid="awv199-AFF18"><sup>18</sup></xref></contrib><contrib contrib-type="author"><name><surname>Teipl</surname><given-names>Stefan</given-names></name><xref ref-type="aff" rid="awv199-AFF19"><sup>19</sup></xref><xref ref-type="aff" rid="awv199-AFF20"><sup>20</sup></xref></contrib><contrib contrib-type="author"><name><surname>Moghekar</surname><given-names>Abhay</given-names></name><xref ref-type="aff" rid="awv199-AFF21"><sup>21</sup></xref></contrib><contrib contrib-type="author"><name><surname>Albert</surname><given-names>Marilyn</given-names></name><xref ref-type="aff" rid="awv199-AFF21"><sup>21</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hu</surname><given-names>William T.</given-names></name><xref ref-type="aff" rid="awv199-AFF22"><sup>22</sup></xref></contrib><contrib contrib-type="author"><name><surname>Monge Argilés</surname><given-names>Jose A.</given-names></name><xref ref-type="aff" rid="awv199-AFF23"><sup>23</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gorostidi</surname><given-names>Ana</given-names></name><xref ref-type="aff" rid="awv199-AFF24"><sup>24</sup></xref></contrib><contrib contrib-type="author"><name><surname>Teunissen</surname><given-names>Charlotte E.</given-names></name><xref ref-type="aff" rid="awv199-AFF25"><sup>25</sup></xref></contrib><contrib contrib-type="author"><name><surname>De Deyn</surname><given-names>Peter P.</given-names></name><xref ref-type="aff" rid="awv199-AFF13"><sup>13</sup></xref><xref ref-type="aff" rid="awv199-AFF14"><sup>14</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hyman</surname><given-names>Bradley T.</given-names></name><xref ref-type="aff" rid="awv199-AFF12"><sup>12</sup></xref></contrib><contrib contrib-type="author"><name><surname>Molinuevo</surname><given-names>Jose L.</given-names></name><xref ref-type="aff" rid="awv199-AFF9"><sup>9</sup></xref></contrib><contrib contrib-type="author"><name><surname>Frisoni</surname><given-names>Giovanni B.</given-names></name><xref ref-type="aff" rid="awv199-AFF7"><sup>7</sup></xref><xref ref-type="aff" rid="awv199-AFF26"><sup>26</sup></xref></contrib><contrib contrib-type="author"><name><surname>Linazasoro</surname><given-names>Gurutz</given-names></name><xref ref-type="aff" rid="awv199-AFF6"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>de Leon</surname><given-names>Mony J.</given-names></name><xref ref-type="aff" rid="awv199-AFF5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>van der Flier</surname><given-names>Wiesje M.</given-names></name><xref ref-type="aff" rid="awv199-AFF4"><sup>4</sup></xref><xref ref-type="aff" rid="awv199-AFF27"><sup>27</sup></xref></contrib><contrib contrib-type="author"><name><surname>Scheltens</surname><given-names>Philip</given-names></name><xref ref-type="aff" rid="awv199-AFF4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Blennow</surname><given-names>Kaj</given-names></name><xref ref-type="aff" rid="awv199-AFF2"><sup>2</sup></xref><xref ref-type="aff" rid="awv199-AFF27"><sup>28</sup></xref></contrib><contrib contrib-type="author"><name><surname>Shaw</surname><given-names>Leslie M.</given-names></name><xref ref-type="aff" rid="awv199-AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Trojanowski</surname><given-names>John Q.</given-names></name><xref ref-type="aff" rid="awv199-AFF1"><sup>1</sup></xref></contrib><on-behalf-of>on behalf of the Alzheimer’s Disease Neuroimaging Initiative</on-behalf-of><aff id="awv199-AFF1">1 Department of Pathology and Laboratory Medicine, Institute on Aging, Centre for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA</aff><aff id="awv199-AFF2">2 Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden</aff><aff id="awv199-AFF3">3 UCL Institute of Neurology, Department of Molecular Neuroscience, Queen Square, London, UK</aff><aff id="awv199-AFF4">4 Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands</aff><aff id="awv199-AFF5">5 Centre for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USA</aff><aff id="awv199-AFF6">6 Department of Neurology, Centre for Research and Advanced Therapies. Fundación CITA-Alzheimer Fundazioa, Donostia/San Sebastián, Spain</aff><aff id="awv199-AFF7">7 IRCCS Centro San Giovanni di Dio FBF, Brescia, Italy</aff><aff id="awv199-AFF8">8 Faculty of Psychology, eCampus University, Novedrate (Como), Italy</aff><aff id="awv199-AFF9">9 Alzheimer’s Disease and Other Cognitive Disorders Unit, Hospital Clinic i Universitari, Barcelona, Spain</aff><aff id="awv199-AFF10">10 Department of Clinical Sciences, Lund University, Lund, Sweden</aff><aff id="awv199-AFF11">11 Memory clinic, Skåne University Hospital, Lund, Sweden</aff><aff id="awv199-AFF12">12 Massachusetts Alzheimer’s Disease Research Centre, Harvard Aging Brain Study, Department of Neurology; Massachusetts General Hospital, Harvard Medical School, Boston, MA,USA</aff><aff id="awv199-AFF13">13 Department of Neurology and Memory Clinic, Hospital Network Antwerp, Middelheim and Hoge Beuken, Belgium</aff><aff id="awv199-AFF14">14 Reference Centre for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Department of Biomedical Sciences, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium</aff><aff id="awv199-AFF15">15 ADx NeuroSciences, Technologiepark 4, Gent, Belgium</aff><aff id="awv199-AFF16">16 Fujirebio Europe nv, Technologiepark 6, Gent, Belgium</aff><aff id="awv199-AFF17">17 AXA Research Fund and UPMC, Université Pierre et Marie Curie, Paris, France</aff><aff id="awv199-AFF18">18 Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, Institut de la Mémoire et de la Maladie d’Alzheimer (IM2A) & Institut du Cerveau et de la Moelle épinière (ICM), Département de Neurologie, Hôpital de la Pitié-Salpétrière, Paris, France</aff><aff id="awv199-AFF19">19 Department of Psychosomatic Medicine, University Medicine Rostock, Rostock, Germany</aff><aff id="awv199-AFF20">20 DZNE, German Centre for Neurodegenerative Diseases, Rostock, Germany</aff><aff id="awv199-AFF21">21 Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA</aff><aff id="awv199-AFF22">22 Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA</aff><aff id="awv199-AFF23">23 Department of Neurology, University General Hospital of Alicante, Alicante, Spain</aff><aff id="awv199-AFF24">24 Neuroscience Unit, Biodonostia Research Institute, San Sebastian, Spain</aff><aff id="awv199-AFF25">25 Neurochemistry Lab and Biobank, Dept. of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Centre Amsterdam, The Netherlands</aff><aff id="awv199-AFF26">26 University Hospitals and University of Geneva, Geneva, Switzerland</aff><aff id="awv199-AFF27">27 Department of Epidemiology/Biostatistics, VU University Medical Centre, USA</aff><aff id="awv199-AFF28">28 The Torsten Söderberg Professorship in Medicine at the Royal Swedish Academy of Sciences, Sweden</aff></contrib-group><author-notes><corresp>Correspondence to: John Q. Trojanowski Department of Pathology and Laboratory Medicine University of Pennsylvania Medical Centre Philadelphia, PA, USA E-mail: <email>trojanow@mail.med.upenn.edu</email></corresp></author-notes><pub-date pub-type="ppub"><month>9</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>28</day><month>7</month><year>2015</year></pub-date><volume>138</volume><issue>9</issue><fpage>2701</fpage><lpage>2715</lpage><history><date date-type="received"><day>27</day><month>1</month><year>2015</year></date><date date-type="rev-recd"><day>10</day><month>4</month><year>2015</year></date><date date-type="accepted"><day>19</day><month>5</month><year>2015</year></date></history><permissions><copyright-statement>© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com</copyright-statement><copyright-year>2015</copyright-year></permissions><abstract abstract-type="precis"><p>In a large multicentre study, Toledo et al. examine core Alzheimer’s disease CSF biomarkers in 1233 cognitively normal subjects aged 40–85 years. Alzheimer disease-like changes in Aβ1-42 are seen as early as middle age, while APOE genotype strongly modifies age-related effects on both Aβ1–42 and phosphorylated/total tau.</p></abstract><abstract abstract-type="graphical"><p><fig id="fig1g" fig-type="featured" position="float"><caption><p>In a large multicentre study, Toledo et al. examine core Alzheimer’s disease CSF biomarkers in 1233 cognitively normal subjects aged 40–85 years. Alzheimer disease-like changes in Aβ1-42 are seen as early as middle age, while APOE genotype strongly modifies age-related effects on both Aβ1–42 and phosphorylated/total tau.</p></caption><graphic xlink:href="awv199fig1g"></graphic></fig></p></abstract><abstract><p>In a large multicentre sample of cognitively normal subjects, as a function of age, gender and <italic>APOE</italic> genotype, we studied the frequency of abnormal cerebrospinal fluid levels of Alzheimer’s disease biomarkers including: total tau, phosphorylated tau and amyloid-β<sub>1-42</sub>. Fifteen cohorts from 12 different centres with either enzyme-linked immunosorbent assays or Luminex® measurements were selected for this study. Each centre sent nine new cerebrospinal fluid aliquots that were used to measure total tau, phosphorylated tau and amyloid-β<sub>1-42</sub> in the Gothenburg laboratory. Seven centres showed a high correlation with the new Gothenburg measurements; therefore, 10 cohorts from these centres are included in the analyses here (1233 healthy control subjects, 40–84 years old). Amyloid-β amyloid status (negative or positive) and neurodegeneration status (negative or positive) was established based on the pathological cerebrospinal fluid Alzheimer’s disease cut-off values for cerebrospinal fluid amyloid-β<sub>1-42</sub> and total tau, respectively. While gender did not affect these biomarker values, <italic>APOE</italic> genotype modified the age-associated changes in cerebrospinal fluid biomarkers such that <italic>APOE</italic> ε4 carriers showed stronger age-related changes in cerebrospinal fluid phosphorylated tau, total tau and amyloid-β<sub>1-42</sub> values and <italic>APOE</italic> ε2 carriers showed the opposite effect. At 40 years of age, 76% of the subjects were classified as amyloid negative, neurodegeneration negative and their frequency decreased to 32% at 85 years. The amyloid-positive neurodegeneration-negative group remained stable. The amyloid-negative neurodegeneration-positive group frequency increased slowly from 1% at 44 years to 16% at 85 years, but its frequency was not affected by <italic>APOE</italic> genotype. The amyloid-positive neurodegeneration-positive frequency increased from 1% at 53 years to 28% at 85 years. Abnormally low cerebrospinal fluid amyloid-β<sub>1-42</sub> levels were already frequent in midlife and <italic>APOE</italic> genotype strongly affects the levels of cerebrospinal fluid amyloid-β<sub>1-42</sub>, phosphorylated tau and total tau across the lifespan without influencing the frequency of subjects with suspected non-amyloid pathology.</p></abstract><kwd-group kwd-group-type="keywords"><kwd>Alzheimer’s disease</kwd><kwd>dementia</kwd><kwd>biomarkers</kwd><kwd>cognitive ageing</kwd><kwd>imaging</kwd></kwd-group><counts><page-count count="15"></page-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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