title: The role of apolipoprotein E (APOE) genotype in early mild cognitive impairment (E-MCI).
abstract: OBJECTIVE
  Our goal was to evaluate the association of APOE with amyloid deposition, cerebrospinal fluid levels (CSF) of Aβ, tau, and p-tau, brain atrophy, cognition and cognitive complaints in E-MCI patients and cognitively healthy older adults (HC) in the ADNI-2 cohort.
  
  
  METHODS
  Two-hundred and nine E-MCI and 123 HC participants from the ADNI-2 cohort were included. We evaluated the impact of diagnostic status (E-MCI vs. HC) and APOE ε4 status (ε4 positive vs. ε4 negative) on cortical amyloid deposition (AV-45/Florbetapir SUVR PET scans), brain atrophy (structural MRI scans processed using voxel-based morphometry and Freesurfer version 5.1), CSF levels of Aβ, tau, and p-tau, and cognitive performance and complaints.
  
  
  RESULTS
  E-MCI participants showed significantly impaired cognition, higher levels of cognitive complaints, greater levels of tau and p-tau, and subcortical and cortical atrophy relative to HC participants (p < 0.05). Cortical amyloid deposition and CSF levels of Aβ were significantly associated with APOE ε4 status but not E-MCI diagnosis, with ε4 positive participants showing more amyloid deposition and lower levels of CSF Aβ than ε4 negative participants. Other effects of APOE ε4 status on cognition and CSF tau levels were also observed.
  
  
  CONCLUSIONS
  APOE ε4 status is associated with amyloid accumulation and lower CSF Aβ, as well as increased CSF tau levels in early prodromal stages of AD (E-MCI) and HC. Alternatively, neurodegeneration, cognitive impairment, and increased complaints are primarily associated with a diagnosis of E-MCI. These findings underscore the importance of considering APOE genotype when evaluating biomarkers in early stages of disease.
authors.affiliation: Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine Indianapolis, IN, USA.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Risacher
authors.forename: Sungeun
authors.initials: S
authors.lastname: Kim
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.forename: Kwangsik
authors.initials: K
authors.lastname: Nho
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
authors.forename: Robert C
authors.initials: RC
authors.lastname: Green
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
authors.forename: Robert A
authors.initials: RA
authors.lastname: Koeppe
authors.forename: William J
authors.initials: WJ
authors.lastname: Jagust
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Saykin
keywords: Alzheimer's disease neuroimaging initiative (ADNI); Florbetapir/AV-45/Amyvid; apolipoprotein E (APOE); cerebrospinal fluid (CSF); early mild cognitive impairment (E-MCI); magnetic resonance imaging (MRI); positron emission tomography (PET)
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