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

Publication ,  Journal Article
Xu, P-T; Li, Y-J; Qin, X-J; Scherzer, CR; Xu, H; Schmechel, DE; Hulette, CM; Ervin, J; Gullans, SR; Haines, J; Pericak-Vance, MA; Gilbert, JR
Published in: Neurobiol Dis
February 2006

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).

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Published In

Neurobiol Dis

DOI

ISSN

0969-9961

Publication Date

February 2006

Volume

21

Issue

2

Start / End Page

256 / 275

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Software
  • Risk Factors
  • Oligonucleotide Array Sequence Analysis
  • Neurology & Neurosurgery
  • Male
  • In Situ Hybridization
  • Humans
  • Hippocampus
  • Genotype
 

Citation

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Xu, P.-T., Li, Y.-J., Qin, X.-J., Scherzer, C. R., Xu, H., Schmechel, D. E., … Gilbert, J. R. (2006). Differences in apolipoprotein E3/3 and E4/4 allele-specific gene expression in hippocampus in Alzheimer disease. Neurobiol Dis, 21(2), 256–275. https://doi.org/10.1016/j.nbd.2005.07.004
Xu, Pu-Ting, Yi-Ju Li, Xue-Jun Qin, Clemens R. Scherzer, Hong Xu, Donald E. Schmechel, Christine M. Hulette, et al. “Differences in apolipoprotein E3/3 and E4/4 allele-specific gene expression in hippocampus in Alzheimer disease.Neurobiol Dis 21, no. 2 (February 2006): 256–75. https://doi.org/10.1016/j.nbd.2005.07.004.
Xu P-T, Li Y-J, Qin X-J, Scherzer CR, Xu H, Schmechel DE, et al. Differences in apolipoprotein E3/3 and E4/4 allele-specific gene expression in hippocampus in Alzheimer disease. Neurobiol Dis. 2006 Feb;21(2):256–75.
Xu, Pu-Ting, et al. “Differences in apolipoprotein E3/3 and E4/4 allele-specific gene expression in hippocampus in Alzheimer disease.Neurobiol Dis, vol. 21, no. 2, Feb. 2006, pp. 256–75. Pubmed, doi:10.1016/j.nbd.2005.07.004.
Xu P-T, Li Y-J, Qin X-J, Scherzer CR, Xu H, Schmechel DE, Hulette CM, Ervin J, Gullans SR, Haines J, Pericak-Vance MA, Gilbert JR. Differences in apolipoprotein E3/3 and E4/4 allele-specific gene expression in hippocampus in Alzheimer disease. Neurobiol Dis. 2006 Feb;21(2):256–275.
Journal cover image

Published In

Neurobiol Dis

DOI

ISSN

0969-9961

Publication Date

February 2006

Volume

21

Issue

2

Start / End Page

256 / 275

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Software
  • Risk Factors
  • Oligonucleotide Array Sequence Analysis
  • Neurology & Neurosurgery
  • Male
  • In Situ Hybridization
  • Humans
  • Hippocampus
  • Genotype