Reduced levels of human apoE4 protein in an animal model of cognitive impairment

Neurobiol Aging. 2011 May;32(5):791-801. doi: 10.1016/j.neurobiolaging.2009.05.011. Epub 2009 Jul 4.


The APOE4 allele is the most common genetic determinant for Alzheimer's disease (AD) in the developed world. APOE genotype specific differences in brain apolipoprotein E protein levels have been observed in numerous studies since the discovery of APOE4's link to AD. Since the human apoE4 targeted replacement mice display characteristics of cognitive impairment we sought to determine if reduced levels of apoE might provide one explanation for this impairment. We developed a novel mass spectrometry method to measure apoE protein levels in plasma. Additionally, we developed an ELISA that replicates the mass spectrometry data and enables the rapid quantitation of apoE in plasma, brain and cerebrospinal fluid. We detected a significant decrease in plasma, brain and cerebrospinal fluid apoE levels in the apoE4 mice compared to apoE2 and E3 mice. We also measured a small (∼19%) decrease in brain apoE levels from aged, non-demented APOE4 carriers. Our findings suggest that a fraction of APOE4-linked AD may be due to insufficient levels of functional apoE required to maintain neuronal health.

Publication types

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

MeSH terms

  • Aged
  • Alzheimer Disease / blood
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / metabolism*
  • Amino Acid Sequence
  • Animals
  • Apolipoprotein E4 / analysis
  • Apolipoprotein E4 / blood
  • Apolipoprotein E4 / cerebrospinal fluid
  • Apolipoprotein E4 / metabolism*
  • Brain / metabolism*
  • Brain Chemistry
  • Cognition Disorders / blood
  • Cognition Disorders / cerebrospinal fluid
  • Cognition Disorders / metabolism*
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Male
  • Mass Spectrometry / methods
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data


  • Apolipoprotein E4