Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease

Monica Garcia-Alloza, Elissa M. Robbins, Sandy X. Zhang-Nunes, Susan M. Purcell, Rebecca A. Betensky, Susan Raju, Claudia Prada, Steven M. Greenberg, Brian J. Bacskai, Matthew P. Frosch

Research output: Contribution to journalArticle

Abstract

Transgenic mice carrying disease-linked forms of genes associated with Alzheimer disease often demonstrate deposition of the β-amyloid as senile plaques and cerebral amyloid angiopathy. We have characterized the natural history of β-amyloid deposition in APPswe/PS1dE9 mice, a particularly aggressive transgenic mouse model generated with mutant transgenes for APP (APPswe: KM594/5NL) and PS1 (dE9: deletion of exon 9). Ex vivo histochemistry showed Aβ deposition by 4 months with a progressive increase in plaque number up to 12 months and a similar increase of Aβ levels. In vivo multiphoton microscopy at weekly intervals showed increasing β-amyloid deposition as CAA and plaques. Although first appearing at an early age, CAA progressed at a significantly slower rate than in the Tg2576 mice. The consistent and early onset of β-amyloid accumulation in the APPswe/PS1dE9 model confirms its utility for studies of biochemical and pathological mechanisms underlying β-amyloid deposition, as well as exploring new therapeutic treatments.

Original languageEnglish (US)
Pages (from-to)516-524
Number of pages9
JournalNeurobiology of Disease
Volume24
Issue number3
DOIs
StatePublished - Dec 2006

Keywords

  • APPswe/PS1dE9
  • Alzheimer disease
  • Amyloid-β
  • Cerebral amyloid angiopathy
  • Transgenic mouse

ASJC Scopus subject areas

  • Neurology

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  • Cite this

    Garcia-Alloza, M., Robbins, E. M., Zhang-Nunes, S. X., Purcell, S. M., Betensky, R. A., Raju, S., Prada, C., Greenberg, S. M., Bacskai, B. J., & Frosch, M. P. (2006). Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease. Neurobiology of Disease, 24(3), 516-524. https://doi.org/10.1016/j.nbd.2006.08.017