title: Alzheimer risk genes modulate the relationship between plasma apoE and cortical PiB binding.
abstract: OBJECTIVE
  We investigated the association between apoE protein plasma levels and brain amyloidosis and the effect of the top 10 Alzheimer disease (AD) risk genes on this association.
  
  
  METHODS
  Our dataset consisted of 18 AD, 52 mild cognitive impairment, and 3 cognitively normal Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) participants with available [(11)C]-Pittsburgh compound B (PiB) and peripheral blood protein data. We used cortical pattern matching to study associations between plasma apoE and cortical PiB binding and the effect of carrier status for the top 10 AD risk genes.
  
  
  RESULTS
  Low plasma apoE was significantly associated with high PiB SUVR, except in the sensorimotor and entorhinal cortex. For BIN1 rs744373, the association was observed only in minor allele carriers. For CD2AP rs9349407 and CR1 rs3818361, the association was preserved only in minor allele noncarriers. We did not find evidence for modulation by CLU, PICALM, ABCA7, BIN1, and MS4A6A.
  
  
  CONCLUSIONS
  Our data show that BIN1 rs744373, CD2AP rs9349407, and CR1 rs3818361 genotypes modulate the association between apoE protein plasma levels and brain amyloidosis, implying a potential epigenetic/downstream interaction.
authors.affiliation: University of California Berkeley (A.L.), Berkeley; Oakland University William Beaumont School of Medicine (K.S.H.), Rochester, MI; Department of Neurology (K.S.H., N.G., A.E.B., E.T., G.C., L.G.A.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Drexel University College of Medicine (L.M.R.), Philadelphia, PA; Northwestern University Feinberg School of Medicine (J.E.), Chicago, IL; Veterans Affairs Greater Los Angeles Healthcare System (E.T., G.C.), Los Angeles, CA; School of Nursing (K.G.), UCLA, Los Angeles, CA; Department of Radiology and Imaging Sciences, Center for Neuroimaging (A.J.S., L.G.A.), Department of Neurology (L.G.A.), and Department of Medical and Molecular Genetics (L.G.A.), School of Medicine, Indiana University, Indianapolis; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), University of Pennsylvania School of Medicine, Philadelphia; Department of Public Health and Neuroscience (W.J.J.), UC Berkeley, CA; and Department of Veterans' Affairs Medical Center (M.W.W.), San Francisco, CA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lazaris
authors.affiliation: University of California Berkeley (A.L.), Berkeley; Oakland University William Beaumont School of Medicine (K.S.H.), Rochester, MI; Department of Neurology (K.S.H., N.G., A.E.B., E.T., G.C., L.G.A.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Drexel University College of Medicine (L.M.R.), Philadelphia, PA; Northwestern University Feinberg School of Medicine (J.E.), Chicago, IL; Veterans Affairs Greater Los Angeles Healthcare System (E.T., G.C.), Los Angeles, CA; School of Nursing (K.G.), UCLA, Los Angeles, CA; Department of Radiology and Imaging Sciences, Center for Neuroimaging (A.J.S., L.G.A.), Department of Neurology (L.G.A.), and Department of Medical and Molecular Genetics (L.G.A.), School of Medicine, Indiana University, Indianapolis; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), University of Pennsylvania School of Medicine, Philadelphia; Department of Public Health and Neuroscience (W.J.J.), UC Berkeley, CA; and Department of Veterans' Affairs Medical Center (M.W.W.), San Francisco, CA.
authors.forename: Kristy S
authors.initials: KS
authors.lastname: Hwang
authors.affiliation: University of California Berkeley (A.L.), Berkeley; Oakland University William Beaumont School of Medicine (K.S.H.), Rochester, MI; Department of Neurology (K.S.H., N.G., A.E.B., E.T., G.C., L.G.A.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Drexel University College of Medicine (L.M.R.), Philadelphia, PA; Northwestern University Feinberg School of Medicine (J.E.), Chicago, IL; Veterans Affairs Greater Los Angeles Healthcare System (E.T., G.C.), Los Angeles, CA; School of Nursing (K.G.), UCLA, Los Angeles, CA; Department of Radiology and Imaging Sciences, Center for Neuroimaging (A.J.S., L.G.A.), Department of Neurology (L.G.A.), and Department of Medical and Molecular Genetics (L.G.A.), School of Medicine, Indiana University, Indianapolis; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), University of Pennsylvania School of Medicine, Philadelphia; Department of Public Health and Neuroscience (W.J.J.), UC Berkeley, CA; and Department of Veterans' Affairs Medical Center (M.W.W.), San Francisco, CA.
authors.forename: Naira
authors.initials: N
authors.lastname: Goukasian
authors.affiliation: University of California Berkeley (A.L.), Berkeley; Oakland University William Beaumont School of Medicine (K.S.H.), Rochester, MI; Department of Neurology (K.S.H., N.G., A.E.B., E.T., G.C., L.G.A.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Drexel University College of Medicine (L.M.R.), Philadelphia, PA; Northwestern University Feinberg School of Medicine (J.E.), Chicago, IL; Veterans Affairs Greater Los Angeles Healthcare System (E.T., G.C.), Los Angeles, CA; School of Nursing (K.G.), UCLA, Los Angeles, CA; Department of Radiology and Imaging Sciences, Center for Neuroimaging (A.J.S., L.G.A.), Department of Neurology (L.G.A.), and Department of Medical and Molecular Genetics (L.G.A.), School of Medicine, Indiana University, Indianapolis; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), University of Pennsylvania School of Medicine, Philadelphia; Department of Public Health and Neuroscience (W.J.J.), UC Berkeley, CA; and Department of Veterans' Affairs Medical Center (M.W.W.), San Francisco, CA.
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Ramirez
authors.affiliation: University of California Berkeley (A.L.), Berkeley; Oakland University William Beaumont School of Medicine (K.S.H.), Rochester, MI; Department of Neurology (K.S.H., N.G., A.E.B., E.T., G.C., L.G.A.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Drexel University College of Medicine (L.M.R.), Philadelphia, PA; Northwestern University Feinberg School of Medicine (J.E.), Chicago, IL; Veterans Affairs Greater Los Angeles Healthcare System (E.T., G.C.), Los Angeles, CA; School of Nursing (K.G.), UCLA, Los Angeles, CA; Department of Radiology and Imaging Sciences, Center for Neuroimaging (A.J.S., L.G.A.), Department of Neurology (L.G.A.), and Department of Medical and Molecular Genetics (L.G.A.), School of Medicine, Indiana University, Indianapolis; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), University of Pennsylvania School of Medicine, Philadelphia; Department of Public Health and Neuroscience (W.J.J.), UC Berkeley, CA; and Department of Veterans' Affairs Medical Center (M.W.W.), San Francisco, CA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Eastman
authors.affiliation: University of California Berkeley (A.L.), Berkeley; Oakland University William Beaumont School of Medicine (K.S.H.), Rochester, MI; Department of Neurology (K.S.H., N.G., A.E.B., E.T., G.C., L.G.A.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Drexel University College of Medicine (L.M.R.), Philadelphia, PA; Northwestern University Feinberg School of Medicine (J.E.), Chicago, IL; Veterans Affairs Greater Los Angeles Healthcare System (E.T., G.C.), Los Angeles, CA; School of Nursing (K.G.), UCLA, Los Angeles, CA; Department of Radiology and Imaging Sciences, Center for Neuroimaging (A.J.S., L.G.A.), Department of Neurology (L.G.A.), and Department of Medical and Molecular Genetics (L.G.A.), School of Medicine, Indiana University, Indianapolis; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), University of Pennsylvania School of Medicine, Philadelphia; Department of Public Health and Neuroscience (W.J.J.), UC Berkeley, CA; and Department of Veterans' Affairs Medical Center (M.W.W.), San Francisco, CA.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Blanken
authors.affiliation: University of California Berkeley (A.L.), Berkeley; Oakland University William Beaumont School of Medicine (K.S.H.), Rochester, MI; Department of Neurology (K.S.H., N.G., A.E.B., E.T., G.C., L.G.A.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Drexel University College of Medicine (L.M.R.), Philadelphia, PA; Northwestern University Feinberg School of Medicine (J.E.), Chicago, IL; Veterans Affairs Greater Los Angeles Healthcare System (E.T., G.C.), Los Angeles, CA; School of Nursing (K.G.), UCLA, Los Angeles, CA; Department of Radiology and Imaging Sciences, Center for Neuroimaging (A.J.S., L.G.A.), Department of Neurology (L.G.A.), and Department of Medical and Molecular Genetics (L.G.A.), School of Medicine, Indiana University, Indianapolis; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), University of Pennsylvania School of Medicine, Philadelphia; Department of Public Health and Neuroscience (W.J.J.), UC Berkeley, CA; and Department of Veterans' Affairs Medical Center (M.W.W.), San Francisco, CA.
authors.forename: Edmond
authors.initials: E
authors.lastname: Teng
authors.affiliation: University of California Berkeley (A.L.), Berkeley; Oakland University William Beaumont School of Medicine (K.S.H.), Rochester, MI; Department of Neurology (K.S.H., N.G., A.E.B., E.T., G.C., L.G.A.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Drexel University College of Medicine (L.M.R.), Philadelphia, PA; Northwestern University Feinberg School of Medicine (J.E.), Chicago, IL; Veterans Affairs Greater Los Angeles Healthcare System (E.T., G.C.), Los Angeles, CA; School of Nursing (K.G.), UCLA, Los Angeles, CA; Department of Radiology and Imaging Sciences, Center for Neuroimaging (A.J.S., L.G.A.), Department of Neurology (L.G.A.), and Department of Medical and Molecular Genetics (L.G.A.), School of Medicine, Indiana University, Indianapolis; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), University of Pennsylvania School of Medicine, Philadelphia; Department of Public Health and Neuroscience (W.J.J.), UC Berkeley, CA; and Department of Veterans' Affairs Medical Center (M.W.W.), San Francisco, CA.
authors.forename: Karen
authors.initials: K
authors.lastname: Gylys
authors.affiliation: University of California Berkeley (A.L.), Berkeley; Oakland University William Beaumont School of Medicine (K.S.H.), Rochester, MI; Department of Neurology (K.S.H., N.G., A.E.B., E.T., G.C., L.G.A.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Drexel University College of Medicine (L.M.R.), Philadelphia, PA; Northwestern University Feinberg School of Medicine (J.E.), Chicago, IL; Veterans Affairs Greater Los Angeles Healthcare System (E.T., G.C.), Los Angeles, CA; School of Nursing (K.G.), UCLA, Los Angeles, CA; Department of Radiology and Imaging Sciences, Center for Neuroimaging (A.J.S., L.G.A.), Department of Neurology (L.G.A.), and Department of Medical and Molecular Genetics (L.G.A.), School of Medicine, Indiana University, Indianapolis; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), University of Pennsylvania School of Medicine, Philadelphia; Department of Public Health and Neuroscience (W.J.J.), UC Berkeley, CA; and Department of Veterans' Affairs Medical Center (M.W.W.), San Francisco, CA.
authors.forename: Greg
authors.initials: G
authors.lastname: Cole
authors.affiliation: University of California Berkeley (A.L.), Berkeley; Oakland University William Beaumont School of Medicine (K.S.H.), Rochester, MI; Department of Neurology (K.S.H., N.G., A.E.B., E.T., G.C., L.G.A.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Drexel University College of Medicine (L.M.R.), Philadelphia, PA; Northwestern University Feinberg School of Medicine (J.E.), Chicago, IL; Veterans Affairs Greater Los Angeles Healthcare System (E.T., G.C.), Los Angeles, CA; School of Nursing (K.G.), UCLA, Los Angeles, CA; Department of Radiology and Imaging Sciences, Center for Neuroimaging (A.J.S., L.G.A.), Department of Neurology (L.G.A.), and Department of Medical and Molecular Genetics (L.G.A.), School of Medicine, Indiana University, Indianapolis; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), University of Pennsylvania School of Medicine, Philadelphia; Department of Public Health and Neuroscience (W.J.J.), UC Berkeley, CA; and Department of Veterans' Affairs Medical Center (M.W.W.), San Francisco, CA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Saykin
authors.affiliation: University of California Berkeley (A.L.), Berkeley; Oakland University William Beaumont School of Medicine (K.S.H.), Rochester, MI; Department of Neurology (K.S.H., N.G., A.E.B., E.T., G.C., L.G.A.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Drexel University College of Medicine (L.M.R.), Philadelphia, PA; Northwestern University Feinberg School of Medicine (J.E.), Chicago, IL; Veterans Affairs Greater Los Angeles Healthcare System (E.T., G.C.), Los Angeles, CA; School of Nursing (K.G.), UCLA, Los Angeles, CA; Department of Radiology and Imaging Sciences, Center for Neuroimaging (A.J.S., L.G.A.), Department of Neurology (L.G.A.), and Department of Medical and Molecular Genetics (L.G.A.), School of Medicine, Indiana University, Indianapolis; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), University of Pennsylvania School of Medicine, Philadelphia; Department of Public Health and Neuroscience (W.J.J.), UC Berkeley, CA; and Department of Veterans' Affairs Medical Center (M.W.W.), San Francisco, CA.
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
authors.affiliation: University of California Berkeley (A.L.), Berkeley; Oakland University William Beaumont School of Medicine (K.S.H.), Rochester, MI; Department of Neurology (K.S.H., N.G., A.E.B., E.T., G.C., L.G.A.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Drexel University College of Medicine (L.M.R.), Philadelphia, PA; Northwestern University Feinberg School of Medicine (J.E.), Chicago, IL; Veterans Affairs Greater Los Angeles Healthcare System (E.T., G.C.), Los Angeles, CA; School of Nursing (K.G.), UCLA, Los Angeles, CA; Department of Radiology and Imaging Sciences, Center for Neuroimaging (A.J.S., L.G.A.), Department of Neurology (L.G.A.), and Department of Medical and Molecular Genetics (L.G.A.), School of Medicine, Indiana University, Indianapolis; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), University of Pennsylvania School of Medicine, Philadelphia; Department of Public Health and Neuroscience (W.J.J.), UC Berkeley, CA; and Department of Veterans' Affairs Medical Center (M.W.W.), San Francisco, CA.
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.affiliation: University of California Berkeley (A.L.), Berkeley; Oakland University William Beaumont School of Medicine (K.S.H.), Rochester, MI; Department of Neurology (K.S.H., N.G., A.E.B., E.T., G.C., L.G.A.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Drexel University College of Medicine (L.M.R.), Philadelphia, PA; Northwestern University Feinberg School of Medicine (J.E.), Chicago, IL; Veterans Affairs Greater Los Angeles Healthcare System (E.T., G.C.), Los Angeles, CA; School of Nursing (K.G.), UCLA, Los Angeles, CA; Department of Radiology and Imaging Sciences, Center for Neuroimaging (A.J.S., L.G.A.), Department of Neurology (L.G.A.), and Department of Medical and Molecular Genetics (L.G.A.), School of Medicine, Indiana University, Indianapolis; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), University of Pennsylvania School of Medicine, Philadelphia; Department of Public Health and Neuroscience (W.J.J.), UC Berkeley, CA; and Department of Veterans' Affairs Medical Center (M.W.W.), San Francisco, CA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Jagust
authors.affiliation: University of California Berkeley (A.L.), Berkeley; Oakland University William Beaumont School of Medicine (K.S.H.), Rochester, MI; Department of Neurology (K.S.H., N.G., A.E.B., E.T., G.C., L.G.A.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Drexel University College of Medicine (L.M.R.), Philadelphia, PA; Northwestern University Feinberg School of Medicine (J.E.), Chicago, IL; Veterans Affairs Greater Los Angeles Healthcare System (E.T., G.C.), Los Angeles, CA; School of Nursing (K.G.), UCLA, Los Angeles, CA; Department of Radiology and Imaging Sciences, Center for Neuroimaging (A.J.S., L.G.A.), Department of Neurology (L.G.A.), and Department of Medical and Molecular Genetics (L.G.A.), School of Medicine, Indiana University, Indianapolis; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), University of Pennsylvania School of Medicine, Philadelphia; Department of Public Health and Neuroscience (W.J.J.), UC Berkeley, CA; and Department of Veterans' Affairs Medical Center (M.W.W.), San Francisco, CA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.affiliation: University of California Berkeley (A.L.), Berkeley; Oakland University William Beaumont School of Medicine (K.S.H.), Rochester, MI; Department of Neurology (K.S.H., N.G., A.E.B., E.T., G.C., L.G.A.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Drexel University College of Medicine (L.M.R.), Philadelphia, PA; Northwestern University Feinberg School of Medicine (J.E.), Chicago, IL; Veterans Affairs Greater Los Angeles Healthcare System (E.T., G.C.), Los Angeles, CA; School of Nursing (K.G.), UCLA, Los Angeles, CA; Department of Radiology and Imaging Sciences, Center for Neuroimaging (A.J.S., L.G.A.), Department of Neurology (L.G.A.), and Department of Medical and Molecular Genetics (L.G.A.), School of Medicine, Indiana University, Indianapolis; Department of Pathology and Laboratory Medicine (L.M.S., J.Q.T.), University of Pennsylvania School of Medicine, Philadelphia; Department of Public Health and Neuroscience (W.J.J.), UC Berkeley, CA; and Department of Veterans' Affairs Medical Center (M.W.W.), San Francisco, CA.
authors.forename: Liana G
authors.initials: LG
authors.lastname: Apostolova