| Literature DB >> 9648880 |
F Oyama1, N Sawamura, K Kobayashi, M Morishima-Kawashima, T Kuramochi, M Ito, T Tomita, K Maruyama, T C Saido, T Iwatsubo, A Capell, J Walter, J Grünberg, Y Ueyama, C Haass, Y Ihara.
Abstract
The N141I missense mutation in presenilin (PS) 2 is tightly linked with a form of autosomal dominant familial Alzheimer's disease (AD) in the Volga German families. We have generated transgenic mouse lines overexpressing human wild-type or mutant PS2 under transcriptional control of the chicken beta-actin promoter. In the brains of transgenic mice, the levels of human PS2 mRNA were found to be five- to 15-fold higher than that of endogenous mouse PS2 mRNA. The amyloid beta-protein (Abeta) 42 levels in the brains of mutant PS2 transgenic mice were higher than those in wild-type PS2 transgenic mice at the age of 2, 5, or 8 months. In addition, the Abeta42 levels appeared to increase steadily in the mutant PS2 transgenic mouse brains from 2 to 8 months of age, whereas there was only a small increase in wild-type transgenic mice between the ages of 5 and 8 months. There was no definite difference in the levels of N-terminal and C-terminal fragments between wild-type and mutant PS2 transgenic mice at the age of 2, 5, or 8 months. These data show a definite effect of the PS2 mutation on an age-dependent increase of Abeta42 content in the brain.Entities:
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Year: 1998 PMID： 9648880 DOI： 10.1046/j.1471-4159.1998.71010313.x
Source DB: PubMed Journal: J Neurochem ISSN： 0022-3042 Impact factor: 5.372