title: Markers of cholesterol transport are associated with amyloid deposition in the brain.
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.
authors.affiliation: Department of Internal Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC, USA. Electronic address: tmhughes@wakehealth.edu.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Hughes
authors.affiliation: Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Oscar L
authors.initials: OL
authors.lastname: Lopez
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Rhobert W
authors.initials: RW
authors.lastname: Evans
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: M Ilyas
authors.initials: MI
authors.lastname: Kamboh
authors.affiliation: Department of Internal Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC, USA.
authors.forename: Jeff D
authors.initials: JD
authors.lastname: Williamson
authors.affiliation: Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Klunk
authors.affiliation: Department of Radiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Chester A
authors.initials: CA
authors.lastname: Mathis
authors.affiliation: Department of Radiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Price
authors.affiliation: Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Ann D
authors.initials: AD
authors.lastname: Cohen
authors.affiliation: Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Beth E
authors.initials: BE
authors.lastname: Snitz
authors.affiliation: University of Virginia School of Medicine, University of Virginia, Charlottesville, VA, USA.
authors.forename: Steven T
authors.initials: ST
authors.lastname: Dekosky
authors.affiliation: Department of Internal Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC, USA.
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Kuller
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D053327:Apolipoprotein E4; D001692:Biological Transport / Q000235:genetics*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D002784:Cholesterol / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D006706:Homeostasis; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D058225:Plaque, Amyloid / Q000235:genetics* / Q000517:prevention & control; D036082:Receptor, EphA1
chemical_list: C411895:ABCA7 protein, human; D018528:ATP-Binding Cassette Transporters; D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D002784:Cholesterol; D036082:Receptor, EphA1
keywords: Alzheimer's disease; Cholesterol; Genes; Imaging; Lipids; Mild cognitive impairment; Oldest old