title: Association of plasma and cortical amyloid beta is modulated by APOE ε4 status.
abstract: BACKGROUND
  Apolipoprotein E (APOE) ε4 allele's role as a modulator of the relationship between soluble plasma amyloid beta (Aβ) and fibrillar brain Aβ measured by Pittsburgh compound B positron emission tomography ([(11)C]PiB PET) has not been assessed.
  
  
  METHODS
  Ninety-six Alzheimer's Disease Neuroimaging Initiative participants with [(11)C]PiB scans and plasma Aβ1-40 and Aβ1-42 measurements at the time of PET scanning were included. Regional and voxelwise analyses of [(11)C]PiB data were used to determine the influence of APOE ε4 allele on association of plasma Aβ1-40, Aβ1-42, and Aβ1-40/Aβ1-42 with [(11)C]PiB uptake.
  
  
  RESULTS
  In APOE ε4- but not ε4+ participants, positive relationships between plasma Aβ1-40/Aβ1-42 and [(11)C]PiB uptake were observed. Modeling the interaction of APOE and plasma Aβ1-40/Aβ1-42 improved the explained variance in [(11)C]PiB binding compared with using APOE and plasma Aβ1-40/Aβ1-42 as separate terms.
  
  
  CONCLUSIONS
  The results suggest that plasma Aβ is a potential Alzheimer's disease biomarker and highlight the importance of genetic variation in interpretation of plasma Aβ levels.
authors.affiliation: Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Shanker
authors.initials: S
authors.lastname: Swaminathan
authors.affiliation: Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Risacher
authors.affiliation: Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Karmen K
authors.initials: KK
authors.lastname: Yoder
authors.affiliation: Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: West
authors.affiliation: Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.affiliation: Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Sungeun
authors.initials: S
authors.lastname: Kim
authors.affiliation: Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Mathematics, Rose-Hulman Institute of Technology, Terre Haute, IN, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Inlow
authors.affiliation: Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
authors.affiliation: Helen Wills Neuroscience Institute, University of California at Berkeley, Berkeley, CA, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Jagust
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Koeppe
authors.affiliation: Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Chester A
authors.initials: CA
authors.lastname: Mathis
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.affiliation: Bristol Myers Squibb Co., Wallingford, CT, USA.
authors.forename: Holly
authors.initials: H
authors.lastname: Soares
authors.affiliation: Department of Neurosciences, University of California at San Diego, San Diego, CA, USA.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
authors.affiliation: Department of Neurology, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.affiliation: Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.affiliation: Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: asaykin@iupui.edu.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Saykin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000000981:diagnostic imaging; D002540:Cerebral Cortex / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000378:metabolism*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D001057:Apolipoproteins E; D010446:Peptide Fragments; D019275:Radiopharmaceuticals; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's Disease Neuroimaging Initiative; Alzheimer's disease; Amyloid beta; Apolipoprotein E; Mild cognitive impairment; Pittsburgh compound B; Plasma amyloid beta; Positron emission tomography
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