title: Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease.
abstract: 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.
authors.affiliation: Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 114 16th Street, Charlestown, MA 02129, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Garcia-Alloza
authors.forename: Elissa M
authors.initials: EM
authors.lastname: Robbins
authors.forename: Sandy X
authors.initials: SX
authors.lastname: Zhang-Nunes
authors.forename: Susan M
authors.initials: SM
authors.lastname: Purcell
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Betensky
authors.forename: Susan
authors.initials: S
authors.lastname: Raju
authors.forename: Claudia
authors.initials: C
authors.lastname: Prada
authors.forename: Steven M
authors.initials: SM
authors.lastname: Greenberg
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Bacskai
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Frosch
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D051379:Mice; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014018:Tissue Distribution
chemical_list: D016564:Amyloid beta-Protein Precursor