Attempts to generate N-AChE-S transgenic mice have thus far been unsuccessful given that over-expression of N-AChE-S is lethal, with almost no embryo passing the morula stage.18 Given that most AD mouse models used to date do not show neuronal death, a major hall-mark of AD, combining existing models with mild N-AChE-S over-expression may lead to a new and more relevant model. This evidence concerns the gene ACHE and Alzheimer disease.