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

P. M. Sullivan, B. Han, F. Liu, B. E. Mace, J. F. Ervin, S. Wu, D. Koger, S. Paul, K. R. Bales

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83 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)791-801
Number of pages11
JournalNeurobiology of Aging
Volume32
Issue number5
DOIs
StatePublished - May 1 2011
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Cerebral spinal fluid
  • Human APOE gene
  • Mass spectrometry
  • Targeted replacement

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    Sullivan, P. M., Han, B., Liu, F., Mace, B. E., Ervin, J. F., Wu, S., Koger, D., Paul, S., & Bales, K. R. (2011). Reduced levels of human apoE4 protein in an animal model of cognitive impairment. Neurobiology of Aging, 32(5), 791-801. https://doi.org/10.1016/j.neurobiolaging.2009.05.011