A genome-wide association meta-analysis of plasma Aβ peptides concentrations in the elderly
Identifieur interne : 000341 ( France/Analysis ); précédent : 000340; suivant : 000342A genome-wide association meta-analysis of plasma Aβ peptides concentrations in the elderly
Auteurs : V. Chouraki [France] ; R. F. A. G. De Bruijn [Pays-Bas] ; J. Chapuis [France] ; J. C. Bis [États-Unis] ; C. Reitz [États-Unis] ; S. Schraen [France] ; C. A. Ibrahim-Verbaas [Pays-Bas] ; B. Grenier-Boley [France] ; C. Delay [France] ; R. Rogers [États-Unis] ; F. Demiautte [France] ; A. Mounier [France] ; A. L. Fitzpatrick [États-Unis] ; C. Berr [France] ; J.-F. Dartigues [France] ; A. G. Uitterlinden [Pays-Bas] ; A. Hofman [Pays-Bas] ; M. Breteler [Pays-Bas, Allemagne] ; J. T. Becker [États-Unis] ; M. Lathrop [France] ; N. Schupf [États-Unis] ; A. Alperovitch [France] ; R. Mayeux [États-Unis] ; C. M. Van Duijn [Pays-Bas] ; L. Buee [France] ; P. Amouyel [France] ; O. L. Lopez [États-Unis] ; M. A. Ikram [Pays-Bas] ; C. Tzourio [France] ; J.-C. Lambert [France]Source :
- Molecular psychiatry [ 1359-4184 ] ; 2014.
Descripteurs français
- KwdFr :
- Cellules HEK293, Fragments peptidiques (sang), Humains, Peptides bêta-amyloïdes (sang), Polymorphisme de nucléotide simple, Population d'origine européenne (génétique), Protéines membranaires (génétique), Protéines membranaires (métabolisme), Précurseur de la protéine bêta-amyloïde (génétique), Précurseur de la protéine bêta-amyloïde (métabolisme), Vieillissement (génétique), Vieillissement (sang), Étude d'association pangénomique.
- MESH :
- Pascal (Inist)
- Wicri :
- topic : Personne âgée.
English descriptors
- KwdEn :
- Aging (blood), Aging (genetics), Alzheimer disease, Amyloid beta-Peptides (blood), Amyloid beta-Protein Precursor (genetics), Amyloid beta-Protein Precursor (metabolism), Elderly, European Continental Ancestry Group (genetics), Genome-Wide Association Study, HEK293 Cells, Humans, Membrane Proteins (genetics), Membrane Proteins (metabolism), Metaanalysis, Peptide Fragments (blood), Polymorphism, Single Nucleotide, Review.
- MESH :
- chemical , blood : Amyloid beta-Peptides, Peptide Fragments.
- blood : Aging.
- genetics : Aging, Amyloid beta-Protein Precursor, European Continental Ancestry Group, Membrane Proteins.
- chemical , metabolism : Amyloid beta-Protein Precursor, Membrane Proteins.
- Genome-Wide Association Study, HEK293 Cells, Humans, Polymorphism, Single Nucleotide.
Abstract
Amyloid beta (Aβ) peptides are the major components of senile plaques, one of the main pathological hallmarks of Alzheimer disease (AD). However, Aβ peptides' functions are not fully understood and seem to be highly pleiotropic. We hypothesized that plasma Aβ peptides concentrations could be a suitable endophenotype for a genome-wide association study (GWAS) designed to (i) identify novel genetic factors involved in amyloid precursor protein metabolism and (ii) highlight relevant Aβ-related physiological and pathophysiological processes. Hence, we performed a genome-wide association meta-analysis of four studies totaling 3 528 healthy individuals of European descent and for whom plasma Aβ1-40 and Aβ1-42 peptides levels had been quantified. Although we did not observe any genome-wide significant locus, we identified 18 suggestive loci (P < 1 × 10-5) Enrichment-pathway analyses revealed canonical pathways mainly involved in neuronal functions, for example, axonal guidance signaling. We also assessed the biological impact of the gene most strongly associated with plasma Aβ1-42 levels (cortexin 3, CTXN3) on APP metabolism in vitro and found that the gene protein was able to modulate Aβ1-42 secretion. In conclusion, our study results suggest that plasma Aβ peptides levels are valid endophenotypes in GWASs and can be used to characterize the metabolism and functions of APP and its metabolites.
Url:
Affiliations:
- Allemagne, France, Pays-Bas, États-Unis
- Aquitaine, District de Cologne, Hauts-de-France, Hollande-Méridionale, Languedoc-Roussillon, Nord-Pas-de-Calais, Nouvelle-Aquitaine, Occitanie (région administrative), Rhénanie-du-Nord-Westphalie, Washington (État), État de New York, Île-de-France
- Bonn, Bordeaux, Leyde, Lille, Montpellier, New York, Paris, Rotterdam, Seattle, Évry (Essonne)
- Université Columbia, Université de Washington
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Pascal:15-0007539Le document en format XML
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Grenier-Boley</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>INSERM U744</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institut pasteur de Lille</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Université Lille-Nord de France</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Delay, C" sort="Delay, C" uniqKey="Delay C" first="C." last="Delay">C. Delay</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>INSERM U744</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institut pasteur de Lille</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Université Lille-Nord de France</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Rogers, R" sort="Rogers, R" uniqKey="Rogers R" first="R." last="Rogers">R. Rogers</name><affiliation wicri:level="4"><inist:fA14 i1="08"><s1>The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University</s1><s2>New York, NY</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>23 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">New York</settlement><region type="state">État de New York</region></placeName><orgName type="university">Université Columbia</orgName></affiliation></author><author><name sortKey="Demiautte, F" sort="Demiautte, F" uniqKey="Demiautte F" first="F." last="Demiautte">F. Demiautte</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>INSERM U744</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institut pasteur de Lille</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Université Lille-Nord de France</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Mounier, A" sort="Mounier, A" uniqKey="Mounier A" first="A." last="Mounier">A. Mounier</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>INSERM U744</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institut pasteur de Lille</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Université Lille-Nord de France</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Fitzpatrick, A L" sort="Fitzpatrick, A L" uniqKey="Fitzpatrick A" first="A. L." last="Fitzpatrick">A. L. Fitzpatrick</name><affiliation wicri:level="4"><inist:fA14 i1="07"><s1>Cardiovascular Health Resarch Unit and Department of Medicine, University of Washington</s1><s2>Seattle, WA</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Seattle</settlement><region type="state">Washington (État)</region></placeName><orgName type="university">Université de Washington</orgName></affiliation></author><author><name sortKey="Berr, C" sort="Berr, C" uniqKey="Berr C" first="C." last="Berr">C. Berr</name><affiliation wicri:level="3"><inist:fA14 i1="13"><s1>INSERM U888, Hôpital La Colombière</s1><s2>Montpellier</s2><s3>FRA</s3><sZ>14 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Languedoc-Roussillon</region><settlement type="city">Montpellier</settlement></placeName></affiliation></author><author><name sortKey="Dartigues, J F" sort="Dartigues, J F" uniqKey="Dartigues J" first="J.-F." last="Dartigues">J.-F. Dartigues</name><affiliation wicri:level="3"><inist:fA14 i1="14"><s1>INSERM U593, Victor Segalen University</s1><s2>Bordeaux</s2><s3>FRA</s3><sZ>15 aut.</sZ><sZ>29 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName></affiliation></author><author><name sortKey="Uitterlinden, A G" sort="Uitterlinden, A G" uniqKey="Uitterlinden A" first="A. G." last="Uitterlinden">A. G. Uitterlinden</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Netherlands Consortium for Healthy Aging</s1><s2>Leiden</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>24 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="15"><s1>Department of Internal medicine, Leiden, Erasmus MC University Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>16 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Hofman, A" sort="Hofman, A" uniqKey="Hofman A" first="A." last="Hofman">A. Hofman</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Epidemiology, Erasmus MC University Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>24 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Netherlands Consortium for Healthy Aging</s1><s2>Leiden</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>24 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Breteler, M" sort="Breteler, M" uniqKey="Breteler M" first="M." last="Breteler">M. Breteler</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Epidemiology, Erasmus MC University Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>24 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="16"><s1>DZNE, German Center for Neurodegenerative Diseases</s1><s2>Bonn</s2><s3>DEU</s3><sZ>18 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Becker, J T" sort="Becker, J T" uniqKey="Becker J" first="J. T." last="Becker">J. T. Becker</name><affiliation wicri:level="1"><inist:fA14 i1="17"><s1>Alzheimer's Disease Research Center, Departments of Neurology, Psychiatry and Psychology, University of Pittsburgh School of Medicine</s1><s2>Pittsburgh, PA</s2><s3>USA</s3><sZ>19 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Pittsburgh, PA</wicri:noRegion></affiliation></author><author><name sortKey="Lathrop, M" sort="Lathrop, M" uniqKey="Lathrop M" first="M." last="Lathrop">M. Lathrop</name><affiliation wicri:level="3"><inist:fA14 i1="18"><s1>Fondation Jean Dausset-Centre d'Etude du Polymorphisme Humain</s1><s2>Paris</s2><s3>FRA</s3><sZ>20 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="19"><s1>Centre National de Genotypage, Institut Genomique, Commissariat à l'énergie Atomique</s1><s2>Evry</s2><s3>FRA</s3><sZ>20 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Évry (Essonne)</settlement></placeName></affiliation></author><author><name sortKey="Schupf, N" sort="Schupf, N" uniqKey="Schupf N" first="N." last="Schupf">N. Schupf</name><affiliation wicri:level="4"><inist:fA14 i1="09"><s1>The Gertrude H. Sergievsky Center, Columbia University</s1><s2>New York, NY</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">New York</settlement><region type="state">État de New York</region></placeName><orgName type="university">Université Columbia</orgName></affiliation></author><author><name sortKey="Alperovitch, A" sort="Alperovitch, A" uniqKey="Alperovitch A" first="A." last="Alperovitch">A. Alperovitch</name><affiliation wicri:level="3"><inist:fA14 i1="20"><s1>INSERM U708</s1><s2>Paris</s2><s3>FRA</s3><sZ>22 aut.</sZ><sZ>29 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Mayeux, R" sort="Mayeux, R" uniqKey="Mayeux R" first="R." last="Mayeux">R. Mayeux</name><affiliation wicri:level="4"><inist:fA14 i1="08"><s1>The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University</s1><s2>New York, NY</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>23 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">New York</settlement><region type="state">État de New York</region></placeName><orgName type="university">Université Columbia</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="21"><s1>The Department of Psychiatry, College of Physicians and Surgeons, Columbia University</s1><s2>New York, NY</s2><s3>USA</s3><sZ>23 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">New York</settlement><region type="state">État de New York</region></placeName><orgName type="university">Université Columbia</orgName></affiliation></author><author><name sortKey="Van Duijn, C M" sort="Van Duijn, C M" uniqKey="Van Duijn C" first="C. M." last="Van Duijn">C. M. Van Duijn</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Epidemiology, Erasmus MC University Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>24 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Netherlands Consortium for Healthy Aging</s1><s2>Leiden</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>24 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Buee, L" sort="Buee, L" uniqKey="Buee L" first="L." last="Buee">L. Buee</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Université Lille-Nord de France</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="11"><s1>Inserm U837, Jean-Pierre Aubert Research Centre</s1><s2>Lille</s2><s3>FRA</s3><sZ>6 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="12"><s1>Centre Hospitalier Regional Universitaire de Lille</s1><s2>Lille</s2><s3>FRA</s3><sZ>6 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Amouyel, P" sort="Amouyel, P" uniqKey="Amouyel P" first="P." last="Amouyel">P. Amouyel</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>INSERM U744</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institut pasteur de Lille</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Université Lille-Nord de France</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="12"><s1>Centre Hospitalier Regional Universitaire de Lille</s1><s2>Lille</s2><s3>FRA</s3><sZ>6 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Lopez, O L" sort="Lopez, O L" uniqKey="Lopez O" first="O. L." last="Lopez">O. L. Lopez</name><affiliation wicri:level="1"><inist:fA14 i1="17"><s1>Alzheimer's Disease Research Center, Departments of Neurology, Psychiatry and Psychology, University of Pittsburgh School of Medicine</s1><s2>Pittsburgh, PA</s2><s3>USA</s3><sZ>19 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Pittsburgh, PA</wicri:noRegion></affiliation></author><author><name sortKey="Ikram, M A" sort="Ikram, M A" uniqKey="Ikram M" first="M. A." last="Ikram">M. A. Ikram</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Epidemiology, Erasmus MC University Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>24 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Department of Neurology, Erasmus MC University Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Netherlands Consortium for Healthy Aging</s1><s2>Leiden</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>24 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="22"><s1>Department of Radiology, Erasmus MC University Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Tzourio, C" sort="Tzourio, C" uniqKey="Tzourio C" first="C." last="Tzourio">C. Tzourio</name><affiliation wicri:level="3"><inist:fA14 i1="14"><s1>INSERM U593, Victor Segalen University</s1><s2>Bordeaux</s2><s3>FRA</s3><sZ>15 aut.</sZ><sZ>29 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="20"><s1>INSERM U708</s1><s2>Paris</s2><s3>FRA</s3><sZ>22 aut.</sZ><sZ>29 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Lambert, J C" sort="Lambert, J C" uniqKey="Lambert J" first="J.-C." last="Lambert">J.-C. 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Chouraki</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>INSERM U744</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institut pasteur de Lille</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Université Lille-Nord de France</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="De Bruijn, R F A G" sort="De Bruijn, R F A G" uniqKey="De Bruijn R" first="R. F. A. G." last="De Bruijn">R. F. A. G. De Bruijn</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Epidemiology, Erasmus MC University Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>24 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Department of Neurology, Erasmus MC University Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Netherlands Consortium for Healthy Aging</s1><s2>Leiden</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>24 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Chapuis, J" sort="Chapuis, J" uniqKey="Chapuis J" first="J." last="Chapuis">J. Chapuis</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>INSERM U744</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institut pasteur de Lille</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Université Lille-Nord de France</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Bis, J C" sort="Bis, J C" uniqKey="Bis J" first="J. C." last="Bis">J. C. Bis</name><affiliation wicri:level="4"><inist:fA14 i1="07"><s1>Cardiovascular Health Resarch Unit and Department of Medicine, University of Washington</s1><s2>Seattle, WA</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Seattle</settlement><region type="state">Washington (État)</region></placeName><orgName type="university">Université de Washington</orgName></affiliation></author><author><name sortKey="Reitz, C" sort="Reitz, C" uniqKey="Reitz C" first="C." last="Reitz">C. Reitz</name><affiliation wicri:level="4"><inist:fA14 i1="08"><s1>The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University</s1><s2>New York, NY</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>23 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">New York</settlement><region type="state">État de New York</region></placeName><orgName type="university">Université Columbia</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="09"><s1>The Gertrude H. Sergievsky Center, Columbia University</s1><s2>New York, NY</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">New York</settlement><region type="state">État de New York</region></placeName><orgName type="university">Université Columbia</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="10"><s1>The Department of Neurology, College of Physicians and Surgeons, Columbia University</s1><s2>New York, NY</s2><s3>USA</s3><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">New York</settlement><region type="state">État de New York</region></placeName><orgName type="university">Université Columbia</orgName></affiliation></author><author><name sortKey="Schraen, S" sort="Schraen, S" uniqKey="Schraen S" first="S." last="Schraen">S. Schraen</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Université Lille-Nord de France</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="11"><s1>Inserm U837, Jean-Pierre Aubert Research Centre</s1><s2>Lille</s2><s3>FRA</s3><sZ>6 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="12"><s1>Centre Hospitalier Regional Universitaire de Lille</s1><s2>Lille</s2><s3>FRA</s3><sZ>6 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Ibrahim Verbaas, C A" sort="Ibrahim Verbaas, C A" uniqKey="Ibrahim Verbaas C" first="C. A." last="Ibrahim-Verbaas">C. A. Ibrahim-Verbaas</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Epidemiology, Erasmus MC University Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>24 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Department of Neurology, Erasmus MC University Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Grenier Boley, B" sort="Grenier Boley, B" uniqKey="Grenier Boley B" first="B." last="Grenier-Boley">B. Grenier-Boley</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>INSERM U744</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institut pasteur de Lille</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Université Lille-Nord de France</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Delay, C" sort="Delay, C" uniqKey="Delay C" first="C." last="Delay">C. Delay</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>INSERM U744</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institut pasteur de Lille</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Université Lille-Nord de France</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Rogers, R" sort="Rogers, R" uniqKey="Rogers R" first="R." last="Rogers">R. Rogers</name><affiliation wicri:level="4"><inist:fA14 i1="08"><s1>The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University</s1><s2>New York, NY</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>23 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">New York</settlement><region type="state">État de New York</region></placeName><orgName type="university">Université Columbia</orgName></affiliation></author><author><name sortKey="Demiautte, F" sort="Demiautte, F" uniqKey="Demiautte F" first="F." last="Demiautte">F. Demiautte</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>INSERM U744</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institut pasteur de Lille</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Université Lille-Nord de France</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Mounier, A" sort="Mounier, A" uniqKey="Mounier A" first="A." last="Mounier">A. Mounier</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>INSERM U744</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institut pasteur de Lille</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Université Lille-Nord de France</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Fitzpatrick, A L" sort="Fitzpatrick, A L" uniqKey="Fitzpatrick A" first="A. L." last="Fitzpatrick">A. L. Fitzpatrick</name><affiliation wicri:level="4"><inist:fA14 i1="07"><s1>Cardiovascular Health Resarch Unit and Department of Medicine, University of Washington</s1><s2>Seattle, WA</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">Seattle</settlement><region type="state">Washington (État)</region></placeName><orgName type="university">Université de Washington</orgName></affiliation></author><author><name sortKey="Berr, C" sort="Berr, C" uniqKey="Berr C" first="C." last="Berr">C. Berr</name><affiliation wicri:level="3"><inist:fA14 i1="13"><s1>INSERM U888, Hôpital La Colombière</s1><s2>Montpellier</s2><s3>FRA</s3><sZ>14 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Languedoc-Roussillon</region><settlement type="city">Montpellier</settlement></placeName></affiliation></author><author><name sortKey="Dartigues, J F" sort="Dartigues, J F" uniqKey="Dartigues J" first="J.-F." last="Dartigues">J.-F. Dartigues</name><affiliation wicri:level="3"><inist:fA14 i1="14"><s1>INSERM U593, Victor Segalen University</s1><s2>Bordeaux</s2><s3>FRA</s3><sZ>15 aut.</sZ><sZ>29 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName></affiliation></author><author><name sortKey="Uitterlinden, A G" sort="Uitterlinden, A G" uniqKey="Uitterlinden A" first="A. G." last="Uitterlinden">A. G. Uitterlinden</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Netherlands Consortium for Healthy Aging</s1><s2>Leiden</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>24 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="15"><s1>Department of Internal medicine, Leiden, Erasmus MC University Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>16 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Hofman, A" sort="Hofman, A" uniqKey="Hofman A" first="A." last="Hofman">A. Hofman</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Epidemiology, Erasmus MC University Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>24 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Netherlands Consortium for Healthy Aging</s1><s2>Leiden</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>24 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Breteler, M" sort="Breteler, M" uniqKey="Breteler M" first="M." last="Breteler">M. Breteler</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Epidemiology, Erasmus MC University Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>24 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="16"><s1>DZNE, German Center for Neurodegenerative Diseases</s1><s2>Bonn</s2><s3>DEU</s3><sZ>18 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Becker, J T" sort="Becker, J T" uniqKey="Becker J" first="J. T." last="Becker">J. T. Becker</name><affiliation wicri:level="1"><inist:fA14 i1="17"><s1>Alzheimer's Disease Research Center, Departments of Neurology, Psychiatry and Psychology, University of Pittsburgh School of Medicine</s1><s2>Pittsburgh, PA</s2><s3>USA</s3><sZ>19 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Pittsburgh, PA</wicri:noRegion></affiliation></author><author><name sortKey="Lathrop, M" sort="Lathrop, M" uniqKey="Lathrop M" first="M." last="Lathrop">M. Lathrop</name><affiliation wicri:level="3"><inist:fA14 i1="18"><s1>Fondation Jean Dausset-Centre d'Etude du Polymorphisme Humain</s1><s2>Paris</s2><s3>FRA</s3><sZ>20 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="19"><s1>Centre National de Genotypage, Institut Genomique, Commissariat à l'énergie Atomique</s1><s2>Evry</s2><s3>FRA</s3><sZ>20 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Évry (Essonne)</settlement></placeName></affiliation></author><author><name sortKey="Schupf, N" sort="Schupf, N" uniqKey="Schupf N" first="N." last="Schupf">N. Schupf</name><affiliation wicri:level="4"><inist:fA14 i1="09"><s1>The Gertrude H. Sergievsky Center, Columbia University</s1><s2>New York, NY</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">New York</settlement><region type="state">État de New York</region></placeName><orgName type="university">Université Columbia</orgName></affiliation></author><author><name sortKey="Alperovitch, A" sort="Alperovitch, A" uniqKey="Alperovitch A" first="A." last="Alperovitch">A. Alperovitch</name><affiliation wicri:level="3"><inist:fA14 i1="20"><s1>INSERM U708</s1><s2>Paris</s2><s3>FRA</s3><sZ>22 aut.</sZ><sZ>29 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Mayeux, R" sort="Mayeux, R" uniqKey="Mayeux R" first="R." last="Mayeux">R. Mayeux</name><affiliation wicri:level="4"><inist:fA14 i1="08"><s1>The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University</s1><s2>New York, NY</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>10 aut.</sZ><sZ>23 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">New York</settlement><region type="state">État de New York</region></placeName><orgName type="university">Université Columbia</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="21"><s1>The Department of Psychiatry, College of Physicians and Surgeons, Columbia University</s1><s2>New York, NY</s2><s3>USA</s3><sZ>23 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><settlement type="city">New York</settlement><region type="state">État de New York</region></placeName><orgName type="university">Université Columbia</orgName></affiliation></author><author><name sortKey="Van Duijn, C M" sort="Van Duijn, C M" uniqKey="Van Duijn C" first="C. M." last="Van Duijn">C. M. Van Duijn</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Epidemiology, Erasmus MC University Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>24 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Netherlands Consortium for Healthy Aging</s1><s2>Leiden</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>24 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Buee, L" sort="Buee, L" uniqKey="Buee L" first="L." last="Buee">L. Buee</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Université Lille-Nord de France</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="11"><s1>Inserm U837, Jean-Pierre Aubert Research Centre</s1><s2>Lille</s2><s3>FRA</s3><sZ>6 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="12"><s1>Centre Hospitalier Regional Universitaire de Lille</s1><s2>Lille</s2><s3>FRA</s3><sZ>6 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Amouyel, P" sort="Amouyel, P" uniqKey="Amouyel P" first="P." last="Amouyel">P. Amouyel</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>INSERM U744</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institut pasteur de Lille</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Université Lille-Nord de France</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="12"><s1>Centre Hospitalier Regional Universitaire de Lille</s1><s2>Lille</s2><s3>FRA</s3><sZ>6 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Lopez, O L" sort="Lopez, O L" uniqKey="Lopez O" first="O. L." last="Lopez">O. L. Lopez</name><affiliation wicri:level="1"><inist:fA14 i1="17"><s1>Alzheimer's Disease Research Center, Departments of Neurology, Psychiatry and Psychology, University of Pittsburgh School of Medicine</s1><s2>Pittsburgh, PA</s2><s3>USA</s3><sZ>19 aut.</sZ><sZ>27 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Pittsburgh, PA</wicri:noRegion></affiliation></author><author><name sortKey="Ikram, M A" sort="Ikram, M A" uniqKey="Ikram M" first="M. A." last="Ikram">M. A. Ikram</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Epidemiology, Erasmus MC University Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>17 aut.</sZ><sZ>18 aut.</sZ><sZ>24 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Department of Neurology, Erasmus MC University Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Netherlands Consortium for Healthy Aging</s1><s2>Leiden</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>16 aut.</sZ><sZ>17 aut.</sZ><sZ>24 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="22"><s1>Department of Radiology, Erasmus MC University Medical Center</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>28 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Tzourio, C" sort="Tzourio, C" uniqKey="Tzourio C" first="C." last="Tzourio">C. Tzourio</name><affiliation wicri:level="3"><inist:fA14 i1="14"><s1>INSERM U593, Victor Segalen University</s1><s2>Bordeaux</s2><s3>FRA</s3><sZ>15 aut.</sZ><sZ>29 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="20"><s1>INSERM U708</s1><s2>Paris</s2><s3>FRA</s3><sZ>22 aut.</sZ><sZ>29 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Lambert, J C" sort="Lambert, J C" uniqKey="Lambert J" first="J.-C." last="Lambert">J.-C. Lambert</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>INSERM U744</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institut pasteur de Lille</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Université Lille-Nord de France</s1><s2>Lille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>25 aut.</sZ><sZ>26 aut.</sZ><sZ>30 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author></analytic><series><title level="j" type="main">Molecular psychiatry</title><title level="j" type="abbreviated">Mol. psychiatry</title><idno type="ISSN">1359-4184</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Molecular psychiatry</title><title level="j" type="abbreviated">Mol. psychiatry</title><idno type="ISSN">1359-4184</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aging (blood)</term><term>Aging (genetics)</term><term>Alzheimer disease</term><term>Amyloid beta-Peptides (blood)</term><term>Amyloid beta-Protein Precursor (genetics)</term><term>Amyloid beta-Protein Precursor (metabolism)</term><term>Elderly</term><term>European Continental Ancestry Group (genetics)</term><term>Genome-Wide Association Study</term><term>HEK293 Cells</term><term>Humans</term><term>Membrane Proteins (genetics)</term><term>Membrane Proteins (metabolism)</term><term>Metaanalysis</term><term>Peptide Fragments (blood)</term><term>Polymorphism, Single Nucleotide</term><term>Review</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Cellules HEK293</term><term>Fragments peptidiques (sang)</term><term>Humains</term><term>Peptides bêta-amyloïdes (sang)</term><term>Polymorphisme de nucléotide simple</term><term>Population d'origine européenne (génétique)</term><term>Protéines membranaires (génétique)</term><term>Protéines membranaires (métabolisme)</term><term>Précurseur de la protéine bêta-amyloïde (génétique)</term><term>Précurseur de la protéine bêta-amyloïde (métabolisme)</term><term>Vieillissement (génétique)</term><term>Vieillissement (sang)</term><term>Étude d'association pangénomique</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Amyloid beta-Peptides</term><term>Peptide Fragments</term></keywords><keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Aging</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Aging</term><term>Amyloid beta-Protein Precursor</term><term>European Continental Ancestry Group</term><term>Membrane Proteins</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Population d'origine européenne</term><term>Protéines membranaires</term><term>Précurseur de la protéine bêta-amyloïde</term><term>Vieillissement</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Amyloid beta-Protein Precursor</term><term>Membrane Proteins</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Protéines membranaires</term><term>Précurseur de la protéine bêta-amyloïde</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Fragments peptidiques</term><term>Peptides bêta-amyloïdes</term><term>Vieillissement</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Genome-Wide Association Study</term><term>HEK293 Cells</term><term>Humans</term><term>Polymorphism, Single Nucleotide</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Cellules HEK293</term><term>Humains</term><term>Métaanalyse</term><term>Article synthèse</term><term>Démence d'Alzheimer</term><term>Personne âgée</term><term>Polymorphisme de nucléotide simple</term><term>Étude d'association pangénomique</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Personne âgée</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Amyloid beta (Aβ) peptides are the major components of senile plaques, one of the main pathological hallmarks of Alzheimer disease (AD). However, Aβ peptides' functions are not fully understood and seem to be highly pleiotropic. We hypothesized that plasma Aβ peptides concentrations could be a suitable endophenotype for a genome-wide association study (GWAS) designed to (i) identify novel genetic factors involved in amyloid precursor protein metabolism and (ii) highlight relevant Aβ-related physiological and pathophysiological processes. Hence, we performed a genome-wide association meta-analysis of four studies totaling 3 528 healthy individuals of European descent and for whom plasma Aβ<sub>1-40</sub> and Aβ<sub>1-42</sub> peptides levels had been quantified. Although we did not observe any genome-wide significant locus, we identified 18 suggestive loci (P < 1 × 10<sup>-5</sup>) Enrichment-pathway analyses revealed canonical pathways mainly involved in neuronal functions, for example, axonal guidance signaling. We also assessed the biological impact of the gene most strongly associated with plasma Aβ<sub>1-42</sub> levels (cortexin 3, CTXN3) on APP metabolism in vitro and found that the gene protein was able to modulate Aβ<sub>1-42</sub> secretion. In conclusion, our study results suggest that plasma Aβ peptides levels are valid endophenotypes in GWASs and can be used to characterize the metabolism and functions of APP and its metabolites.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>France</li><li>Pays-Bas</li><li>États-Unis</li></country><region><li>Aquitaine</li><li>District de Cologne</li><li>Hauts-de-France</li><li>Hollande-Méridionale</li><li>Languedoc-Roussillon</li><li>Nord-Pas-de-Calais</li><li>Nouvelle-Aquitaine</li><li>Occitanie (région administrative)</li><li>Rhénanie-du-Nord-Westphalie</li><li>Washington (État)</li><li>État de New York</li><li>Île-de-France</li></region><settlement><li>Bonn</li><li>Bordeaux</li><li>Leyde</li><li>Lille</li><li>Montpellier</li><li>New York</li><li>Paris</li><li>Rotterdam</li><li>Seattle</li><li>Évry (Essonne)</li></settlement><orgName><li>Université Columbia</li><li>Université de Washington</li></orgName></list><tree><country name="France"><region name="Hauts-de-France"><name sortKey="Chouraki, V" sort="Chouraki, V" uniqKey="Chouraki V" first="V." last="Chouraki">V. Chouraki</name></region><name sortKey="Alperovitch, A" sort="Alperovitch, A" uniqKey="Alperovitch A" first="A." last="Alperovitch">A. Alperovitch</name><name sortKey="Amouyel, P" sort="Amouyel, P" uniqKey="Amouyel P" first="P." last="Amouyel">P. Amouyel</name><name sortKey="Amouyel, P" sort="Amouyel, P" uniqKey="Amouyel P" first="P." last="Amouyel">P. Amouyel</name><name sortKey="Amouyel, P" sort="Amouyel, P" uniqKey="Amouyel P" first="P." last="Amouyel">P. Amouyel</name><name sortKey="Amouyel, P" sort="Amouyel, P" uniqKey="Amouyel P" first="P." last="Amouyel">P. Amouyel</name><name sortKey="Berr, C" sort="Berr, C" uniqKey="Berr C" first="C." last="Berr">C. Berr</name><name sortKey="Buee, L" sort="Buee, L" uniqKey="Buee L" first="L." last="Buee">L. Buee</name><name sortKey="Buee, L" sort="Buee, L" uniqKey="Buee L" first="L." last="Buee">L. Buee</name><name sortKey="Buee, L" sort="Buee, L" uniqKey="Buee L" first="L." last="Buee">L. Buee</name><name sortKey="Chapuis, J" sort="Chapuis, J" uniqKey="Chapuis J" first="J." last="Chapuis">J. Chapuis</name><name sortKey="Chapuis, J" sort="Chapuis, J" uniqKey="Chapuis J" first="J." last="Chapuis">J. Chapuis</name><name sortKey="Chapuis, J" sort="Chapuis, J" uniqKey="Chapuis J" first="J." last="Chapuis">J. Chapuis</name><name sortKey="Chouraki, V" sort="Chouraki, V" uniqKey="Chouraki V" first="V." last="Chouraki">V. Chouraki</name><name sortKey="Chouraki, V" sort="Chouraki, V" uniqKey="Chouraki V" first="V." last="Chouraki">V. Chouraki</name><name sortKey="Dartigues, J F" sort="Dartigues, J F" uniqKey="Dartigues J" first="J.-F." last="Dartigues">J.-F. Dartigues</name><name sortKey="Delay, C" sort="Delay, C" uniqKey="Delay C" first="C." last="Delay">C. Delay</name><name sortKey="Delay, C" sort="Delay, C" uniqKey="Delay C" first="C." last="Delay">C. Delay</name><name sortKey="Delay, C" sort="Delay, C" uniqKey="Delay C" first="C." last="Delay">C. Delay</name><name sortKey="Demiautte, F" sort="Demiautte, F" uniqKey="Demiautte F" first="F." last="Demiautte">F. Demiautte</name><name sortKey="Demiautte, F" sort="Demiautte, F" uniqKey="Demiautte F" first="F." last="Demiautte">F. Demiautte</name><name sortKey="Demiautte, F" sort="Demiautte, F" uniqKey="Demiautte F" first="F." last="Demiautte">F. Demiautte</name><name sortKey="Grenier Boley, B" sort="Grenier Boley, B" uniqKey="Grenier Boley B" first="B." last="Grenier-Boley">B. Grenier-Boley</name><name sortKey="Grenier Boley, B" sort="Grenier Boley, B" uniqKey="Grenier Boley B" first="B." last="Grenier-Boley">B. Grenier-Boley</name><name sortKey="Grenier Boley, B" sort="Grenier Boley, B" uniqKey="Grenier Boley B" first="B." last="Grenier-Boley">B. Grenier-Boley</name><name sortKey="Lambert, J C" sort="Lambert, J C" uniqKey="Lambert J" first="J.-C." last="Lambert">J.-C. Lambert</name><name sortKey="Lambert, J C" sort="Lambert, J C" uniqKey="Lambert J" first="J.-C." last="Lambert">J.-C. Lambert</name><name sortKey="Lambert, J C" sort="Lambert, J C" uniqKey="Lambert J" first="J.-C." last="Lambert">J.-C. Lambert</name><name sortKey="Lathrop, M" sort="Lathrop, M" uniqKey="Lathrop M" first="M." last="Lathrop">M. Lathrop</name><name sortKey="Lathrop, M" sort="Lathrop, M" uniqKey="Lathrop M" first="M." last="Lathrop">M. Lathrop</name><name sortKey="Mounier, A" sort="Mounier, A" uniqKey="Mounier A" first="A." last="Mounier">A. Mounier</name><name sortKey="Mounier, A" sort="Mounier, A" uniqKey="Mounier A" first="A." last="Mounier">A. Mounier</name><name sortKey="Mounier, A" sort="Mounier, A" uniqKey="Mounier A" first="A." last="Mounier">A. Mounier</name><name sortKey="Schraen, S" sort="Schraen, S" uniqKey="Schraen S" first="S." last="Schraen">S. Schraen</name><name sortKey="Schraen, S" sort="Schraen, S" uniqKey="Schraen S" first="S." last="Schraen">S. Schraen</name><name sortKey="Schraen, S" sort="Schraen, S" uniqKey="Schraen S" first="S." last="Schraen">S. Schraen</name><name sortKey="Tzourio, C" sort="Tzourio, C" uniqKey="Tzourio C" first="C." last="Tzourio">C. Tzourio</name><name sortKey="Tzourio, C" sort="Tzourio, C" uniqKey="Tzourio C" first="C." last="Tzourio">C. Tzourio</name></country><country name="Pays-Bas"><region name="Hollande-Méridionale"><name sortKey="De Bruijn, R F A G" sort="De Bruijn, R F A G" uniqKey="De Bruijn R" first="R. F. A. G." last="De Bruijn">R. F. A. G. De Bruijn</name></region><name sortKey="Breteler, M" sort="Breteler, M" uniqKey="Breteler M" first="M." last="Breteler">M. Breteler</name><name sortKey="De Bruijn, R F A G" sort="De Bruijn, R F A G" uniqKey="De Bruijn R" first="R. F. A. G." last="De Bruijn">R. F. A. G. De Bruijn</name><name sortKey="De Bruijn, R F A G" sort="De Bruijn, R F A G" uniqKey="De Bruijn R" first="R. F. A. G." last="De Bruijn">R. F. A. G. De Bruijn</name><name sortKey="Hofman, A" sort="Hofman, A" uniqKey="Hofman A" first="A." last="Hofman">A. Hofman</name><name sortKey="Hofman, A" sort="Hofman, A" uniqKey="Hofman A" first="A." last="Hofman">A. Hofman</name><name sortKey="Ibrahim Verbaas, C A" sort="Ibrahim Verbaas, C A" uniqKey="Ibrahim Verbaas C" first="C. A." last="Ibrahim-Verbaas">C. A. Ibrahim-Verbaas</name><name sortKey="Ibrahim Verbaas, C A" sort="Ibrahim Verbaas, C A" uniqKey="Ibrahim Verbaas C" first="C. A." last="Ibrahim-Verbaas">C. A. Ibrahim-Verbaas</name><name sortKey="Ikram, M A" sort="Ikram, M A" uniqKey="Ikram M" first="M. A." last="Ikram">M. A. Ikram</name><name sortKey="Ikram, M A" sort="Ikram, M A" uniqKey="Ikram M" first="M. A." last="Ikram">M. A. Ikram</name><name sortKey="Ikram, M A" sort="Ikram, M A" uniqKey="Ikram M" first="M. A." last="Ikram">M. A. Ikram</name><name sortKey="Ikram, M A" sort="Ikram, M A" uniqKey="Ikram M" first="M. A." last="Ikram">M. A. Ikram</name><name sortKey="Uitterlinden, A G" sort="Uitterlinden, A G" uniqKey="Uitterlinden A" first="A. G." last="Uitterlinden">A. G. Uitterlinden</name><name sortKey="Uitterlinden, A G" sort="Uitterlinden, A G" uniqKey="Uitterlinden A" first="A. G." last="Uitterlinden">A. G. Uitterlinden</name><name sortKey="Van Duijn, C M" sort="Van Duijn, C M" uniqKey="Van Duijn C" first="C. M." last="Van Duijn">C. M. Van Duijn</name><name sortKey="Van Duijn, C M" sort="Van Duijn, C M" uniqKey="Van Duijn C" first="C. M." last="Van Duijn">C. M. Van Duijn</name></country><country name="États-Unis"><region name="Washington (État)"><name sortKey="Bis, J C" sort="Bis, J C" uniqKey="Bis J" first="J. C." last="Bis">J. C. Bis</name></region><name sortKey="Becker, J T" sort="Becker, J T" uniqKey="Becker J" first="J. T." last="Becker">J. T. Becker</name><name sortKey="Fitzpatrick, A L" sort="Fitzpatrick, A L" uniqKey="Fitzpatrick A" first="A. L." last="Fitzpatrick">A. L. Fitzpatrick</name><name sortKey="Lopez, O L" sort="Lopez, O L" uniqKey="Lopez O" first="O. L." last="Lopez">O. L. Lopez</name><name sortKey="Mayeux, R" sort="Mayeux, R" uniqKey="Mayeux R" first="R." last="Mayeux">R. Mayeux</name><name sortKey="Mayeux, R" sort="Mayeux, R" uniqKey="Mayeux R" first="R." last="Mayeux">R. Mayeux</name><name sortKey="Reitz, C" sort="Reitz, C" uniqKey="Reitz C" first="C." last="Reitz">C. Reitz</name><name sortKey="Reitz, C" sort="Reitz, C" uniqKey="Reitz C" first="C." last="Reitz">C. Reitz</name><name sortKey="Reitz, C" sort="Reitz, C" uniqKey="Reitz C" first="C." last="Reitz">C. Reitz</name><name sortKey="Rogers, R" sort="Rogers, R" uniqKey="Rogers R" first="R." last="Rogers">R. Rogers</name><name sortKey="Schupf, N" sort="Schupf, N" uniqKey="Schupf N" first="N." last="Schupf">N. 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