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Amyloid Precursor Protein Processing and Aβ 42 Deposition in a Transgenic Mouse Model of Alzheimer Disease

K. Johnson-Wood, M. Lee, R. Motter, K. Hu, G. Gordon, R. Barbour, K. Khan, M. Gordon, H. Tan, D. Games, I. Lieberburg, D. Schenk, P. Seubert and L. McConlogue
Proceedings of the National Academy of Sciences of the United States of America
Vol. 94, No. 4 (Feb. 18, 1997), pp. 1550-1555
Stable URL: http://www.jstor.org/stable/41369
Page Count: 6
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Amyloid Precursor Protein Processing and Aβ 42 Deposition in a Transgenic Mouse Model of Alzheimer Disease
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Abstract

The PDAPP transgenic mouse, which over-expresses human amyloid precursor protein (APP717V→ F), has been shown to develop much of the pathology associated with Alzheimer disease. In this report, levels of APP and its amyloidogenic metabolites were measured in brain regions of transgenic mice between 4 and 18 months of age. While absolute levels of APP expression likely contribute to the rate of amyloid β -peptide (Aβ ) deposition, regionally specific factors also seem important, as homozygotic mice express APP levels in pathologically unaffected regions in excess of that measured in certain amyloid plaque-prone regions of heterozygotic mice. Regional levels of APp and APP-β were nearly constant at all ages, while Aβ levels dramatically and predictably increased in brain regions undergoing histochemically confirmed amyloidosis, most notably in the cortex and hippocampus. In hippocampus, Aβ concentrations increase 17-fold between the ages of 4 and 8 months, and by 18 months of age are over 500-fold that at 4 months, reaching an average level in excess of 20 nmol of Aβ per g of tissue. Aβ 1-42 constitutes the vast majority of the depositing Aβ species. The similarities observed between the PDAPP mouse and human Alzheimer disease with regard to Aβ 42 deposition occurring in a temporally and regionally specific fashion further validate the use of the model in understanding processes related to the disease.

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