Markers of cholesterol transport are associated with amyloid deposition in the brain.
Identifieur interne : 002258 ( Main/Exploration ); précédent : 002257; suivant : 002259Markers of cholesterol transport are associated with amyloid deposition in the brain.
Auteurs : Timothy M. Hughes [États-Unis] ; Oscar L. Lopez [États-Unis] ; Rhobert W. Evans [États-Unis] ; M Ilyas Kamboh [États-Unis] ; Jeff D. Williamson [États-Unis] ; William E. Klunk [États-Unis] ; Chester A. Mathis [États-Unis] ; Julie C. Price [États-Unis] ; Ann D. Cohen [États-Unis] ; Beth E. Snitz [États-Unis] ; Steven T. Dekosky [États-Unis] ; Lewis H. Kuller [États-Unis]Source :
- Neurobiology of aging [ 1558-1497 ] ; 2014.
Descripteurs français
- KwdFr :
- Apolipoprotéine E4, Cholestérol (métabolisme), Encéphale (anatomopathologie), Encéphale (métabolisme), Femelle, Homéostasie, Humains, Maladie d'Alzheimer (), Maladie d'Alzheimer (génétique), Mâle, Peptides bêta-amyloïdes (métabolisme), Plaque amyloïde (), Plaque amyloïde (génétique), Récepteur EphA1, Sujet âgé, Sujet âgé de 80 ans ou plus, Thérapie moléculaire ciblée, Transport biologique (génétique), Transporteurs ABC, Études de cohortes.
- MESH :
- anatomopathologie : Encéphale.
- génétique : Maladie d'Alzheimer, Plaque amyloïde, Transport biologique.
- métabolisme : Cholestérol, Encéphale, Peptides bêta-amyloïdes.
- Apolipoprotéine E4, Femelle, Homéostasie, Humains, Maladie d'Alzheimer, Mâle, Plaque amyloïde, Récepteur EphA1, Sujet âgé, Sujet âgé de 80 ans ou plus, Thérapie moléculaire ciblée, Transporteurs ABC, Études de cohortes.
English descriptors
- KwdEn :
- ATP-Binding Cassette Transporters, Aged, Aged, 80 and over, Alzheimer Disease (genetics), Alzheimer Disease (prevention & control), Amyloid beta-Peptides (metabolism), Apolipoprotein E4, Biological Transport (genetics), Brain (metabolism), Brain (pathology), Cholesterol (metabolism), Cohort Studies, Female, Homeostasis, Humans, Male, Molecular Targeted Therapy, Plaque, Amyloid (genetics), Plaque, Amyloid (prevention & control), Receptor, EphA1.
- MESH :
- chemical , metabolism : Amyloid beta-Peptides, Cholesterol.
- genetics : Alzheimer Disease, Biological Transport, Plaque, Amyloid.
- metabolism : Brain.
- pathology : Brain.
- prevention & control : Alzheimer Disease, Plaque, Amyloid.
- ATP-Binding Cassette Transporters, Aged, Aged, 80 and over, Apolipoprotein E4, Cohort Studies, Female, Homeostasis, Humans, Male, Molecular Targeted Therapy, Receptor, EphA1.
Abstract
Cholesterol is implicated in the development of late-onset Alzheimer's disease (AD). We sought to determine the associations between beta amyloid (Aβ) plaque deposition in vivo using Pittsburgh compound B (PiB) and several indices of cholesterol homeostasis (i.e., total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein E (ApoE), clusterin, oxysterol metabolites of cholesterol, and previously reported genes associated with late-onset AD) in 175 nondemented elderly subjects. High Aβ deposition was associated significantly with a lower Mini-Mental State Examination score (<27 points, p = 0.04), high systolic blood pressure (p = 0.04), carrying the apolipoprotein E epsilon 4 allele (p < 0.01), and lower plasma ApoE levels (p = 0.02), and variation in the ABCA7 (p = 0.02) and EPHA1 genes (p = 0.02). Cholesterol measures were not related to Aβ deposition in this cohort of nondemented elderly adults. However, plasma and genetic factors relating to cholesterol transport were associated with Aβ deposition in the brain. A better understanding of cholesterol transport mechanisms may lead to the design of potential targets for the prevention of Aβ deposition in the brain.
DOI: 10.1016/j.neurobiolaging.2013.09.040
PubMed: 24199960
Affiliations:
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Le document en format XML
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Hughes</name><affiliation wicri:level="2"><nlm:affiliation>Department of Internal Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC, USA. Electronic address: tmhughes@wakehealth.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Internal Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Lopez, Oscar L" sort="Lopez, Oscar L" uniqKey="Lopez O" first="Oscar L" last="Lopez">Oscar L. Lopez</name><affiliation wicri:level="4"><nlm:affiliation>Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Evans, Rhobert W" sort="Evans, Rhobert W" uniqKey="Evans R" first="Rhobert W" last="Evans">Rhobert W. Evans</name><affiliation wicri:level="4"><nlm:affiliation>Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Kamboh, M Ilyas" sort="Kamboh, M Ilyas" uniqKey="Kamboh M" first="M Ilyas" last="Kamboh">M Ilyas Kamboh</name><affiliation wicri:level="4"><nlm:affiliation>Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Williamson, Jeff D" sort="Williamson, Jeff D" uniqKey="Williamson J" first="Jeff D" last="Williamson">Jeff D. Williamson</name><affiliation wicri:level="2"><nlm:affiliation>Department of Internal Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Internal Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Klunk, William E" sort="Klunk, William E" uniqKey="Klunk W" first="William E" last="Klunk">William E. Klunk</name><affiliation wicri:level="4"><nlm:affiliation>Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Mathis, Chester A" sort="Mathis, Chester A" uniqKey="Mathis C" first="Chester A" last="Mathis">Chester A. Mathis</name><affiliation wicri:level="4"><nlm:affiliation>Department of Radiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Radiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Price, Julie C" sort="Price, Julie C" uniqKey="Price J" first="Julie C" last="Price">Julie C. Price</name><affiliation wicri:level="4"><nlm:affiliation>Department of Radiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Radiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Cohen, Ann D" sort="Cohen, Ann D" uniqKey="Cohen A" first="Ann D" last="Cohen">Ann D. Cohen</name><affiliation wicri:level="4"><nlm:affiliation>Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Snitz, Beth E" sort="Snitz, Beth E" uniqKey="Snitz B" first="Beth E" last="Snitz">Beth E. Snitz</name><affiliation wicri:level="4"><nlm:affiliation>Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Dekosky, Steven T" sort="Dekosky, Steven T" uniqKey="Dekosky S" first="Steven T" last="Dekosky">Steven T. Dekosky</name><affiliation wicri:level="2"><nlm:affiliation>University of Virginia School of Medicine, University of Virginia, Charlottesville, VA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>University of Virginia School of Medicine, University of Virginia, Charlottesville, VA</wicri:regionArea><placeName><region type="state">Virginie</region></placeName></affiliation></author><author><name sortKey="Kuller, Lewis H" sort="Kuller, Lewis H" uniqKey="Kuller L" first="Lewis H" last="Kuller">Lewis H. Kuller</name><affiliation wicri:level="2"><nlm:affiliation>Department of Internal Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Internal Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author></analytic><series><title level="j">Neurobiology of aging</title><idno type="eISSN">1558-1497</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>ATP-Binding Cassette Transporters</term><term>Aged</term><term>Aged, 80 and over</term><term>Alzheimer Disease (genetics)</term><term>Alzheimer Disease (prevention & control)</term><term>Amyloid beta-Peptides (metabolism)</term><term>Apolipoprotein E4</term><term>Biological Transport (genetics)</term><term>Brain (metabolism)</term><term>Brain (pathology)</term><term>Cholesterol (metabolism)</term><term>Cohort Studies</term><term>Female</term><term>Homeostasis</term><term>Humans</term><term>Male</term><term>Molecular Targeted Therapy</term><term>Plaque, Amyloid (genetics)</term><term>Plaque, Amyloid (prevention & control)</term><term>Receptor, EphA1</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Apolipoprotéine E4</term><term>Cholestérol (métabolisme)</term><term>Encéphale (anatomopathologie)</term><term>Encéphale (métabolisme)</term><term>Femelle</term><term>Homéostasie</term><term>Humains</term><term>Maladie d'Alzheimer ()</term><term>Maladie d'Alzheimer (génétique)</term><term>Mâle</term><term>Peptides bêta-amyloïdes (métabolisme)</term><term>Plaque amyloïde ()</term><term>Plaque amyloïde (génétique)</term><term>Récepteur EphA1</term><term>Sujet âgé</term><term>Sujet âgé de 80 ans ou plus</term><term>Thérapie moléculaire ciblée</term><term>Transport biologique (génétique)</term><term>Transporteurs ABC</term><term>Études de cohortes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Amyloid beta-Peptides</term><term>Cholesterol</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Encéphale</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Alzheimer Disease</term><term>Biological Transport</term><term>Plaque, Amyloid</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Maladie d'Alzheimer</term><term>Plaque amyloïde</term><term>Transport biologique</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Brain</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cholestérol</term><term>Encéphale</term><term>Peptides bêta-amyloïdes</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Brain</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Alzheimer Disease</term><term>Plaque, Amyloid</term></keywords><keywords scheme="MESH" xml:lang="en"><term>ATP-Binding Cassette Transporters</term><term>Aged</term><term>Aged, 80 and over</term><term>Apolipoprotein E4</term><term>Cohort Studies</term><term>Female</term><term>Homeostasis</term><term>Humans</term><term>Male</term><term>Molecular Targeted Therapy</term><term>Receptor, EphA1</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Apolipoprotéine E4</term><term>Femelle</term><term>Homéostasie</term><term>Humains</term><term>Maladie d'Alzheimer</term><term>Mâle</term><term>Plaque amyloïde</term><term>Récepteur EphA1</term><term>Sujet âgé</term><term>Sujet âgé de 80 ans ou plus</term><term>Thérapie moléculaire ciblée</term><term>Transporteurs ABC</term><term>Études de cohortes</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Cholesterol is implicated in the development of late-onset Alzheimer's disease (AD). We sought to determine the associations between beta amyloid (Aβ) plaque deposition in vivo using Pittsburgh compound B (PiB) and several indices of cholesterol homeostasis (i.e., total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein E (ApoE), clusterin, oxysterol metabolites of cholesterol, and previously reported genes associated with late-onset AD) in 175 nondemented elderly subjects. High Aβ deposition was associated significantly with a lower Mini-Mental State Examination score (<27 points, p = 0.04), high systolic blood pressure (p = 0.04), carrying the apolipoprotein E epsilon 4 allele (p < 0.01), and lower plasma ApoE levels (p = 0.02), and variation in the ABCA7 (p = 0.02) and EPHA1 genes (p = 0.02). Cholesterol measures were not related to Aβ deposition in this cohort of nondemented elderly adults. However, plasma and genetic factors relating to cholesterol transport were associated with Aβ deposition in the brain. A better understanding of cholesterol transport mechanisms may lead to the design of potential targets for the prevention of Aβ deposition in the brain.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Caroline du Nord</li><li>Pennsylvanie</li><li>Virginie</li></region><settlement><li>Pittsburgh</li></settlement><orgName><li>Université de Pittsburgh</li></orgName></list><tree><country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Hughes, Timothy M" sort="Hughes, Timothy M" uniqKey="Hughes T" first="Timothy M" last="Hughes">Timothy M. Hughes</name></region><name sortKey="Cohen, Ann D" sort="Cohen, Ann D" uniqKey="Cohen A" first="Ann D" last="Cohen">Ann D. Cohen</name><name sortKey="Dekosky, Steven T" sort="Dekosky, Steven T" uniqKey="Dekosky S" first="Steven T" last="Dekosky">Steven T. Dekosky</name><name sortKey="Evans, Rhobert W" sort="Evans, Rhobert W" uniqKey="Evans R" first="Rhobert W" last="Evans">Rhobert W. Evans</name><name sortKey="Kamboh, M Ilyas" sort="Kamboh, M Ilyas" uniqKey="Kamboh M" first="M Ilyas" last="Kamboh">M Ilyas Kamboh</name><name sortKey="Klunk, William E" sort="Klunk, William E" uniqKey="Klunk W" first="William E" last="Klunk">William E. Klunk</name><name sortKey="Kuller, Lewis H" sort="Kuller, Lewis H" uniqKey="Kuller L" first="Lewis H" last="Kuller">Lewis H. Kuller</name><name sortKey="Lopez, Oscar L" sort="Lopez, Oscar L" uniqKey="Lopez O" first="Oscar L" last="Lopez">Oscar L. Lopez</name><name sortKey="Mathis, Chester A" sort="Mathis, Chester A" uniqKey="Mathis C" first="Chester A" last="Mathis">Chester A. Mathis</name><name sortKey="Price, Julie C" sort="Price, Julie C" uniqKey="Price J" first="Julie C" last="Price">Julie C. Price</name><name sortKey="Snitz, Beth E" sort="Snitz, Beth E" uniqKey="Snitz B" first="Beth E" last="Snitz">Beth E. Snitz</name><name sortKey="Williamson, Jeff D" sort="Williamson, Jeff D" uniqKey="Williamson J" first="Jeff D" last="Williamson">Jeff D. Williamson</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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