title: APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern.
abstract: BACKGROUND
  This study assessed apolipoprotein E (APOE) ε4 carrier status effects on Alzheimer's disease imaging and cerebrospinal fluid (CSF) biomarkers in cognitively normal older adults with significant memory concerns (SMC).
  
  
  METHODS
  Cognitively normal, SMC, and early mild cognitive impairment participants from Alzheimer's Disease Neuroimaging Initiative were divided by APOE ε4 carrier status. Diagnostic and APOE effects were evaluated with emphasis on SMC. Additional analyses in SMC evaluated the effect of the interaction between APOE and [(18)F]Florbetapir amyloid positivity on CSF biomarkers.
  
  
  RESULTS
  SMC ε4+ showed greater amyloid deposition than SMC ε4-, but no hypometabolism or medial temporal lobe (MTL) atrophy. SMC ε4+ showed lower amyloid beta 1-42 and higher tau/p-tau than ε4-, which was most abnormal in APOE ε4+ and cerebral amyloid positive SMC.
  
  
  CONCLUSIONS
  SMC APOE ε4+ show abnormal changes in amyloid and tau biomarkers, but no hypometabolism or MTL neurodegeneration, reflecting the at-risk nature of the SMC group and the importance of APOE in mediating this risk.
authors.affiliation: Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Risacher
authors.affiliation: Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana Alzheimer Disease Center, 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: Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Kwangsik
authors.initials: K
authors.lastname: Nho
authors.affiliation: Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
authors.affiliation: Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana Alzheimer Disease Center, 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: Department of Neurology, Mayo Clinic, Rochester MN, USA.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester MN, USA.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: Department of Public Health Sciences, Division of Biostatistics, University of California-Davis, Davis, CA, USA.
authors.forename: Laurel A
authors.initials: LA
authors.lastname: Beckett
authors.affiliation: Department of Neurology, University of California-San Diego, San Diego, CA, USA.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Koeppe
authors.affiliation: Department of Neurology, University of California-Berkeley, Berkeley, CA, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Jagust
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: Departments of Radiology, Medicine and Psychiatry, University of California-San Francisco, San Francisco, CA, USA; Department of Veterans Affairs Medical Center, San Francisco, CA, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.affiliation: Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, 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: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D053327:Apolipoprotein E4 / Q000235:genetics*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000175:diagnosis; D005260:Female; D005838:Genotype; D064368:Healthy Volunteers; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology*; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; D016875:tau Proteins
keywords: ADNI; APOE; Alzheimer's Disease Neuroimaging Initiative; Apolipoprotein E; CSF; Cerebrospinal fluid; FDG; Neuroimaging; PET; SCD; SMC; Significant memory concern; Structural magnetic resonance imaging (MRI); Subjective cognitive decline; [(18)F]Florbetapir PET; [(18)F]Fluorodeoxyglucose