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Apoptosis is an important process in the variety of different biological system including cell death and embryonic development. Inappropriate apoptosis is implicated in many human diseases such as Alzheimer's disease. Central component of the machinery of apoptosis program in neurons of patients with Alzheimer's disease includes proteins of caspases and Bcl-2 families. We examined whether endogenous protein levels of caspases and Bcl-2 families are expressed in a differential manner during the embryonic and postnatal development of BDF1 strain. Here, all four proteins with caspases-3, -9, Bcl-2 and Bax were highly expressed between embryonic day 19 and 1 week age of early postnatal development, but thereafter the expression dramatically declined. These patterns are needed to compare the proteins in the brains of APPsw-transgenic mice that are expected to be expressed highly in the brain of adult mice. Thus, the results are useful to understand fundamentally the mechanisms of the apoptotic changes during the embryonic and postnatal development of Alzheimer's model mice.

Apoptosis is an important process in the variety of different biological system including cell death and embryonic development. Inappropriate apoptosis is implicated in many human diseases such as Alzheimer's disease. Central component of the machinery of apoptosis program in neurons of patients with Alzheimer's disease includes proteins of caspases and Bcl-2 families. We examined whether endogenous protein levels of caspases and Bcl-2 families are expressed in a differential manner during the embryonic and postnatal development of BDF1 strain. Here, all four proteins with caspases-3, -9, Bcl-2 and Bax were highly expressed between embryonic day 19 and 1 week age of early postnatal development, but thereafter the expression dramatically declined. These patterns are needed to compare the proteins in the brains of APPsw-transgenic mice that are expected to be expressed highly in the brain of adult mice. Thus, the results are useful to understand fundamentally the mechanisms of the apoptotic changes during the embryonic and postnatal development of Alzheimer's model mice.

Mutations in the APP gene lead to enhanced cleavage by the beta- and gamma-secretase, and increased Abeta formation, which are tightly associated with Alzheimer's disease (AD)-like neuropathological changes. To examine whether depositions of Abeta by APP mutations are increased, and if this is associated with potential pathogenic phenotypes, the APPsw was expressed in a transgenic line under the control of the neuron-specific enolase (NSE) promoter. A behavioral dysfunction was shown at 12 months, and intensive staining bands, with APP and Abeta-42 antibodies, were visible in the brains of transgenic mice. Of the MAPK family, both JNK and p38 were activated in the brains of transgenic mice, whereas there was no significant activation of the ERK. In parallel, tau phosphorylation was also enhanced in the transgenic relative to the control mice. Moreover, the Cox-2 levels, from Western blot and immunostaining, were increased in the brains of the transgenic line. Furthermore, there were significant caspase-3- and TUNEL-stained nuclei in the transgenic line compared to the age-matched control mice. Thus, these results suggest that NSE-controlled APPsw transgenic mice appear to be a more relevant model in neuropathological phenotypes of AD, and thus could be useful in developing new therapeutic treatments for targeting the aberrant phenotypes that appear in these mice.

Alzheimer's disease (AD) occurs when neurons in the memory and cognition regions of the brain are accompanied by an accumulation of the long amyloid beta-proteins of the 39 to 43 amino acids derived from the amyloid precursor protein (APP) by cleavage with beta- and gamma-secretase. An increased production of Abeta-42 by mutation of PS2 genes promotes caspase expression and is associated with the Cox-2 found in the brain of AD patients. To address this question in vivo, we expressed the human mutant PS2 (hPS2m) (N141I) as well as wild PS2 (hPS2w) as a control in transgenic (Tg) mice under control of the neuron-specific enolase (NSE) promoter. Water maze tests were used to demonstrate the behavioral defect; dot blot, Western blot, and immunohistochemical analyses were performed on the brain with the hPS2, Abeta-42, caspase-3, and Cox-2 antibody. We concluded that 1) Tg mice showed a behavioral dysfunction in the water maze test, 2) levels of hPS2, Abeta-42, caspase-3, and Cox-2 expression were modulated in the brains of both Tg mice, 3) dense staining with antibody to hPS2, Abeta-42, caspase-3, and Cox-2 was visible in the brains of Tg mice compared with age-matched control mice, and 4) distinguishable AD phenotypes between hPS2w- and hPS2m-Tg mice did not appear. These results suggest that an elevation of Abeta-42 by overexpression of hPS2 and mutation of hPS2m might induce the behavioral deficit and caspase-3 and Cox-2 induction, which could be useful in the therapeutic testing of compounds to have considerable clinical effects.