References
Query Results -- Details
MGI Accession ID: MGI:1098936
J Number: J:43788
Other Accession IDs:
Title: Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins.
Authors: Borchelt DR; Ratovitski T; van Lare J; Lee MK; Gonzales V; Jenkins NA; Copeland NG; Price DL; Sisodia SS
Journal: Neuron
Volume: 19
Issue: 4
Date: 1997 Oct
Year: 1997
Pages: 939-45
Review Status: Peer Reviewed
Abstract:
Missense mutations in two related genes, termed presenilin 1 (PS1) and presenilin 2 (PS2), cause dementia in a subset of early-onset familial Alzheimer's disease (FAD) pedigrees. In a variety of experimental in vitro and in vivo settings, FAD-linked presenilin variants influence the processing of the amyloid precursor protein (APP), leading to elevated levels of the highly fibrillogenic Abeta1-42 peptides that are preferentially deposited in the brains of Alzheimer Disease (AD) patients. In this report, we demonstrate that transgenic animals that coexpress a FAD-linked human PS1 variant (A246E) and a chimeric mouse/human APP harboring mutations linked to Swedish FAD kindreds (APP swe) develop numerous amyloid deposits much earlier than age-matched mice expressing APP swe and wild-type Hu PS1 or APP swe alone. These results provide evidence for the view that one pathogenic mechanism by which FAD-linked mutant PS1 causes AD is to accelerate the rate of beta-amyloid deposition in brain.
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