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Human apolipoprotein E redistributes fibrillar amyloid deposition in Tg-SwDI mice.

Publication ,  Journal Article
Xu, F; Vitek, MP; Colton, CA; Previti, ML; Gharkholonarehe, N; Davis, J; Van Nostrand, WE
Published in: J Neurosci
May 14, 2008

Human apolipoprotein (ApoE) genotype influences the development of Alzheimer's disease and cerebral amyloid angiopathy (CAA). Specific mutations within the amyloid-beta protein (Abeta) peptide have been identified that cause familial forms of CAA. However, the effect of APOE genotype on accumulation of CAA mutant Abeta in brain is not well understood. In the present study, we determined how human ApoE3 or ApoE4 influence cerebral Abeta accumulation in transgenic mice (Tg-SwDI) that accumulate human Dutch/Iowa (E22Q/D23N) CAA mutant Abeta in brain, primarily in the form of fibrillar cerebral microvascular amyloid. Using Tg-SwDI mice bred onto a human APOE3/3 or human APOE4/4 background, we found that both human ApoE3 and ApoE4 proteins led to a strong reduction in the amount of cerebral microvascular amyloid with an unexpected concomitant appearance of extensive fibrillar parenchymal plaque amyloid. There was strong colocalization of all ApoE proteins with fibrillar amyloid deposits in the mice. In Tg-SwDI/hAPOE3/3 and Tg-SwDI/hAPOE4/4 mice, there was no change in the levels of total Abeta(40) and Abeta(42) or in the amounts of soluble and insoluble Abeta in brain compared with Tg-SwDI mice on the endogenous mouse APOE background. The shift from primarily cerebral microvascular amyloid to parenchymal plaque amyloid in Tg-SwDI/hAPOE3/3 and Tg-SwDI/hAPOE4/4 mice resulted in a parallel shift in the association of activated microglia. These findings indicate that human ApoE has a strong influence on the spatial development of human Dutch/Iowa CAA mutant amyloid accumulation in mouse brain and that microglial activation is in response to the spatial accumulation of fibrillar amyloid.

Duke Scholars

Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

May 14, 2008

Volume

28

Issue

20

Start / End Page

5312 / 5320

Location

United States

Related Subject Headings

  • Protein Isoforms
  • Plaque, Amyloid
  • Neuropil
  • Neurons
  • Neurology & Neurosurgery
  • Microglia
  • Microcirculation
  • Mice, Transgenic
  • Mice
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Xu, F., Vitek, M. P., Colton, C. A., Previti, M. L., Gharkholonarehe, N., Davis, J., & Van Nostrand, W. E. (2008). Human apolipoprotein E redistributes fibrillar amyloid deposition in Tg-SwDI mice. J Neurosci, 28(20), 5312–5320. https://doi.org/10.1523/JNEUROSCI.1042-08.2008
Xu, Feng, Michael P. Vitek, Carol A. Colton, Mary Lou Previti, Nastaran Gharkholonarehe, Judianne Davis, and William E. Van Nostrand. “Human apolipoprotein E redistributes fibrillar amyloid deposition in Tg-SwDI mice.J Neurosci 28, no. 20 (May 14, 2008): 5312–20. https://doi.org/10.1523/JNEUROSCI.1042-08.2008.
Xu F, Vitek MP, Colton CA, Previti ML, Gharkholonarehe N, Davis J, et al. Human apolipoprotein E redistributes fibrillar amyloid deposition in Tg-SwDI mice. J Neurosci. 2008 May 14;28(20):5312–20.
Xu, Feng, et al. “Human apolipoprotein E redistributes fibrillar amyloid deposition in Tg-SwDI mice.J Neurosci, vol. 28, no. 20, May 2008, pp. 5312–20. Pubmed, doi:10.1523/JNEUROSCI.1042-08.2008.
Xu F, Vitek MP, Colton CA, Previti ML, Gharkholonarehe N, Davis J, Van Nostrand WE. Human apolipoprotein E redistributes fibrillar amyloid deposition in Tg-SwDI mice. J Neurosci. 2008 May 14;28(20):5312–5320.

Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

May 14, 2008

Volume

28

Issue

20

Start / End Page

5312 / 5320

Location

United States

Related Subject Headings

  • Protein Isoforms
  • Plaque, Amyloid
  • Neuropil
  • Neurons
  • Neurology & Neurosurgery
  • Microglia
  • Microcirculation
  • Mice, Transgenic
  • Mice
  • Humans