APOE genotype and early β-amyloid accumulation in older adults without dementia

Neurology. 2017 Sep 5;89(10):1028-1034. doi: 10.1212/WNL.0000000000004336. Epub 2017 Aug 9.


Objective: To clarify associations between APOE ε4 allele and age on longitudinal rates of β-amyloid (Aβ) accumulation within Aβ+ and Aβ- older individuals without dementia.

Methods: We analyzed 595 older adults without dementia classified cross-sectionally as Aβ- (n = 325) and Aβ+ (n = 270) using longitudinal florbetapir PET. The influence of age and APOE genotype on longitudinal accumulation of Aβ was examined with linear mixed models.

Results: APOE ε4 and older age were associated with higher risk of being classified as Aβ+ at baseline. The annual rate of Aβ accumulation was significantly greater than zero for Aβ- ε3 (0.0021 ± 0.0007 standardized uptake value ratio [SUVR] units) and Aβ- ε4 (0.0044 ± 0.0010 SUVR units), as well as Aβ+ ε3 (0.0141 ± 0.0019 SUVR units) and Aβ+ ε4 (0.0126 ± 0.0018 SUVR units). Aβ accumulation was significantly faster in Aβ- ε4 compared to Aβ- ε3 and Aβ- ε2. Rates of Aβ accumulation did not differ significantly between Aβ+ APOE groups. Older age was associated with higher rates of Aβ accumulation in the Aβ- group.

Conclusions: APOE ε4 carriage and older age were predictors of longitudinal Aβ accumulation within the Aβ- group but not the Aβ+ group. APOE ε2 carriage was protective against longitudinal Aβ accumulation within the Aβ- group. APOE genotype in conjunction with chronologic age may aid in participant selection for primary prevention trials aimed at halting Aβ accumulation before abnormal levels are reached.

MeSH terms

  • Aged
  • Aging / genetics*
  • Aging / metabolism*
  • Amyloid beta-Peptides / metabolism*
  • Aniline Compounds
  • Apolipoprotein E2 / genetics*
  • Apolipoprotein E3 / genetics
  • Apolipoprotein E4 / genetics*
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Cross-Sectional Studies
  • Ethylene Glycols
  • Female
  • Heterozygote
  • Humans
  • Linear Models
  • Male
  • Positron-Emission Tomography
  • Radiopharmaceuticals
  • Risk Factors
  • Superior Sagittal Sinus


  • Amyloid beta-Peptides
  • Aniline Compounds
  • Apolipoprotein E2
  • Apolipoprotein E3
  • Apolipoprotein E4
  • Ethylene Glycols
  • Radiopharmaceuticals
  • florbetapir