Relative effect of APOE ε4 on neuroimaging biomarker changes across the lifespan

Neurology. 2016 Oct 18;87(16):1696-1703. doi: 10.1212/WNL.0000000000003234. Epub 2016 Sep 28.


Objective: To provide a comprehensive understanding of APOE ε4 effects across the lifespan on the 3 main neuroimaging biomarkers.

Methods: Two hundred seven community-dwelling, cognitively normal APOE ε4 carriers and noncarriers aged 20-87 years were involved in this study. They underwent structural MRI, fluorodeoxyglucose-PET, and florbetapir-PET scans. The effects of APOE, age, and APOE × age interaction were assessed voxel-wise for each modality.

Results: There was no significant effect of APOE or APOE × age interaction on gray matter volume and glucose metabolism, although decreases with age tended to be stronger in noncarriers than in carriers. In contrast, β-amyloid (Aβ) deposition was significantly higher in carriers compared with noncarriers in a largely distributed network, and there was a significant APOE × age interaction such that Aβ deposition increased nonlinearly with age in APOE ε4 carriers only.

Conclusions: Our findings highlight a differential effect of APOE ε4 on amyloid vs neurodegeneration biomarkers. APOE ε4 mainly influences Aβ deposition, while the effects on gray matter volume and glucose metabolism are at best subtle.

Clinicaltrialsgov identifier: NCT01638949.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / genetics*
  • Aging / metabolism
  • Aging / pathology*
  • Amyloid beta-Peptides / metabolism
  • Aniline Compounds
  • Apolipoprotein E4 / genetics*
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Ethylene Glycols
  • Female
  • Fluorodeoxyglucose F18
  • Glucose / metabolism
  • Gray Matter / diagnostic imaging
  • Gray Matter / metabolism
  • Heterozygote
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Nonlinear Dynamics
  • Organ Size
  • Positron-Emission Tomography*
  • Radiopharmaceuticals
  • Young Adult


  • Amyloid beta-Peptides
  • Aniline Compounds
  • Apolipoprotein E4
  • Ethylene Glycols
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • florbetapir
  • Glucose

Associated data