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

Transgenic mice carrying disease-linked forms of genes associated with Alzheimer disease often demonstrate deposition of the beta-amyloid as senile plaques and cerebral amyloid angiopathy. We have characterized the natural history of beta-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 Abeta deposition by 4 months with a progressive increase in plaque number up to 12 months and a similar increase of Abeta levels. In vivo multiphoton microscopy at weekly intervals showed increasing beta-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 beta-amyloid accumulation in the APPswe/PS1dE9 model confirms its utility for studies of biochemical and pathological mechanisms underlying beta-amyloid deposition, as well as exploring new therapeutic treatments.