Skip to main content

Human apolipoprotein E2 promotes parenchymal amyloid deposition and neuronal loss in vasculotropic mutant amyloid-β protein Tg-SwDI mice.

Publication ,  Journal Article
Xu, F; Vitek, MP; Colton, CA; Previti, ML; Davis, J; Van Nostrand, WE
Published in: J Alzheimers Dis
2012

Human apolipoprotein (ApoE) genotype influences the development of Alzheimer's disease and cerebral amyloid angiopathy (CAA), where the ε4 allele increases and the ε2 allele decreases the risk for developing disease. Specific mutations within the amyloid-β (Aβ) peptide have been identified that cause familial forms of CAA. However, the influence of APOE genotype on accumulation of CAA mutant Aβ in brain is not well understood. Earlier, we showed that human ApoE4 redistributes fibrillar amyloid deposition from the cerebral microvasculature to parenchymal plaques in Tg-SwDI mice, a model that accumulates human Dutch/Iowa (E22Q/D23N) CAA mutant Aβ in brain (Xu et al., J Neurosci 28, 5312-5320, 2008). Human ApoE2 can reduce Aβ pathology in transgenic models of parenchymal plaques. Here we determined if human ApoE2 can influence the location and severity of amyloid pathology in Tg-SwDI mice. Comparing Tg-SwDI mice bred onto a human APOE2/2 or human APOE4/4 background, we found there was no change in the brain levels of total Aβ(40) and Aβ(42) compared to mice on the endogenous mouse APOE background. In Tg-SwDI mice on either human APOE background, there was a similarly strong reduction in the levels of microvascular CAA and emergence of extensive parenchymal plaque amyloid. In both Tg-SwDI-hAPOE2/2 and Tg-SwDI-hAPOE4/4 mice, the distribution of ApoE proteins and neuronal loss were associated with parenchymal amyloid plaques. These findings suggest that compared with human ApoE4, human ApoE2 does not beneficially influence the quantitative or spatial accumulation of human Dutch/Iowa CAA mutant amyloid or associated pathology in transgenic mice.

Duke Scholars

Published In

J Alzheimers Dis

DOI

EISSN

1875-8908

Publication Date

2012

Volume

31

Issue

2

Start / End Page

359 / 369

Location

Netherlands

Related Subject Headings

  • Plaque, Amyloid
  • Neurons
  • Neurology & Neurosurgery
  • Mutation
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Humans
  • Cerebral Amyloid Angiopathy
  • Apolipoprotein E4
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Xu, F., Vitek, M. P., Colton, C. A., Previti, M. L., Davis, J., & Van Nostrand, W. E. (2012). Human apolipoprotein E2 promotes parenchymal amyloid deposition and neuronal loss in vasculotropic mutant amyloid-β protein Tg-SwDI mice. J Alzheimers Dis, 31(2), 359–369. https://doi.org/10.3233/JAD-2012-120421
Xu, Feng, Michael P. Vitek, Carol A. Colton, Mary Lou Previti, Judianne Davis, and William E. Van Nostrand. “Human apolipoprotein E2 promotes parenchymal amyloid deposition and neuronal loss in vasculotropic mutant amyloid-β protein Tg-SwDI mice.J Alzheimers Dis 31, no. 2 (2012): 359–69. https://doi.org/10.3233/JAD-2012-120421.
Xu F, Vitek MP, Colton CA, Previti ML, Davis J, Van Nostrand WE. Human apolipoprotein E2 promotes parenchymal amyloid deposition and neuronal loss in vasculotropic mutant amyloid-β protein Tg-SwDI mice. J Alzheimers Dis. 2012;31(2):359–69.
Xu, Feng, et al. “Human apolipoprotein E2 promotes parenchymal amyloid deposition and neuronal loss in vasculotropic mutant amyloid-β protein Tg-SwDI mice.J Alzheimers Dis, vol. 31, no. 2, 2012, pp. 359–69. Pubmed, doi:10.3233/JAD-2012-120421.
Xu F, Vitek MP, Colton CA, Previti ML, Davis J, Van Nostrand WE. Human apolipoprotein E2 promotes parenchymal amyloid deposition and neuronal loss in vasculotropic mutant amyloid-β protein Tg-SwDI mice. J Alzheimers Dis. 2012;31(2):359–369.

Published In

J Alzheimers Dis

DOI

EISSN

1875-8908

Publication Date

2012

Volume

31

Issue

2

Start / End Page

359 / 369

Location

Netherlands

Related Subject Headings

  • Plaque, Amyloid
  • Neurons
  • Neurology & Neurosurgery
  • Mutation
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Humans
  • Cerebral Amyloid Angiopathy
  • Apolipoprotein E4