APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern

Alzheimers Dement. 2015 Dec;11(12):1417-1429. doi: 10.1016/j.jalz.2015.03.003. Epub 2015 May 7.


Introduction: 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.

Discussion: 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.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / cerebrospinal fluid
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Apolipoprotein E4 / genetics*
  • Biomarkers / cerebrospinal fluid
  • Brain / metabolism*
  • Brain / pathology
  • Cognitive Dysfunction / cerebrospinal fluid
  • Cognitive Dysfunction / diagnosis
  • Female
  • Genotype
  • Healthy Volunteers
  • Heterozygote
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Memory / physiology*
  • Neuropsychological Tests
  • Positron-Emission Tomography
  • tau Proteins / cerebrospinal fluid*


  • Amyloid beta-Peptides
  • Apolipoprotein E4
  • Biomarkers
  • tau Proteins