Differences in apolipoprotein E3/3 and E4/4 allele-specific gene expression in hippocampus in Alzheimer disease

Pu Ting Xu, Yi Ju Li, Xue Jun Qin, Clemens R. Scherzer, Hong Xu, Donald E. Schmechel, Christine M. Hulette, John Ervin, Steven R. Gullans, Jonathan Haines, Margaret A. Pericak-Vance, John R. Gilbert

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Apolipoprotein E4 (APOE4) allele is a major risk factor for late-onset familial and sporadic Alzheimer disease (AD). The mechanism of action of APOE in the etiology of AD remains unclear. Using gene expression (microarray) analysis of human hippocampus from APOE3/3 AD and APOE4/4 AD cases, we found different gene transcription patterns between APOE4/4 and APOE3/3 AD cases. The expression of APOE4/4 alleles, in comparison to APOE3/3, is associated with upregulation of multiple gene transcripts encoding cell growth suppresser or arrest, signal transduction, myelinogenesis, cell adhesion and migration, heavy metal metabolism and detoxification. Whereas the APOE4 gene expression is associated with downregulation of gene transcripts involved in mitochondrial oxidative phosphorylation and energy metabolism, synaptic vesicle docking and fusing, and synaptic plasticity compared to APOE3. These mechanisms may contribute increased risk for AD and for cognitive dysfunction in AD patients who carry the APOE4 allele(s).

Original languageEnglish (US)
Pages (from-to)256-275
Number of pages20
JournalNeurobiology of Disease
Volume21
Issue number2
DOIs
StatePublished - Feb 1 2006

Keywords

  • Alzheimer disease
  • Apolipoprotein E
  • Apoptosis
  • Gene expression
  • Microarray
  • Signal pathways

ASJC Scopus subject areas

  • Neurology

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  • Cite this

    Xu, P. T., Li, Y. J., Qin, X. J., Scherzer, C. R., Xu, H., Schmechel, D. E., Hulette, C. M., Ervin, J., Gullans, S. R., Haines, J., Pericak-Vance, M. A., & Gilbert, J. R. (2006). Differences in apolipoprotein E3/3 and E4/4 allele-specific gene expression in hippocampus in Alzheimer disease. Neurobiology of Disease, 21(2), 256-275. https://doi.org/10.1016/j.nbd.2005.07.004