Transgenic mice overexpressing the three major neuronal isoforms of the human amyloid precursor protein (APP), APP695, APP751, APP770 may provide an animal model for the analysis of the mechanisms and risk factors leading to amyloid deposition in Alzheimer's disease (AD) and Downs syndrome (DS). We have therefore generated transgenic mice expressing these isoforms under the control of the strong metallothionin promoter. Although we can demonstrate expression of transgenic APP in several tissues including brain, expression levels never exceeded those of the endogenous mouse APP. So far we have not been able to detect pathological changes resembling those of AD and DS. However we could demonstrate significant changes in spatial navigation tasks and motor behavior in the transgenic mice. The question remains open whether overexpression of APP is sufficient to induce Alzheimer pathology.