The APOE ε4 Allele Is Associated With Lower Selenium Levels in the Brain: Implications for Alzheimer's Disease

ACS Chem Neurosci. 2017 Jul 19;8(7):1459-1464. doi: 10.1021/acschemneuro.7b00014. Epub 2017 May 3.


The antioxidant activity of selenium, which is mainly conferred by its incorporation into dedicated selenoproteins, has been suggested as a possible neuroprotective approach for mitigating neuronal loss in Alzheimer's disease. However, there is inconsistent information with respect to selenium levels in the Alzheimer's disease brain. We examined the concentration and cellular compartmentalization of selenium in the temporal cortex of Alzheimer's disease and control brain tissue. We found that Alzheimer's disease was associated with decreased selenium concentration in both soluble (i.e., cytosolic) and insoluble (i.e., plaques and tangles) fractions of brain homogenates. The presence of the APOE ε4 allele correlated with lower total selenium levels in the temporal cortex and a higher concentration of soluble selenium. Additionally, we found that age significantly contributed to lower selenium concentrations in the peripheral membrane-bound and vesicular fractions. Our findings suggest a relevant interaction between APOE ε4 and selenium delivery into brain, and show changes in cellular selenium distribution in the Alzheimer's disease brain.

Keywords: APOE ε4; Alzheimer’s disease; Selenium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / genetics
  • Aging / metabolism
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism*
  • Apolipoprotein E4 / genetics*
  • Brain Chemistry / genetics*
  • Cytosol / chemistry
  • Female
  • Heterozygote
  • Humans
  • Male
  • Mass Spectrometry
  • Neurofibrillary Tangles / chemistry
  • Plaque, Amyloid / chemistry
  • Selenium / analysis*
  • Temporal Lobe / chemistry*


  • Apolipoprotein E4
  • Selenium