The present invention provides for a transgenic non-human animal whose
cells contain a DNA sequence comprising: (a) a nerve tissue specific
promoter operatively linked to a DNA sequence which encodes amyloid-beta
peptide alcohol dehydrogenase (ABAD), and (b) a nerve tissue specific
promoter operatively linked to a DNA sequence encoding a mutant human
amyloid precursor protein hAPP695, hAPP751 and hAPP770 bearing mutations
linked to familial Alzheimer's disease in humans, wherein the non-human
animal exhibits at least one phenotype from the group consisting of:
reduced basal synaptic transmission; inhibited synaptic plasticity;
increased neuronal stress; elevated 4-hydroxynonenal in cerebral cortex;
increased heme oxygenase type I in cerebral cortex; decreased
synaptophysin in cerebral cortex; decreased micortubule-associated
protein 2 in cerebral cortex; and increased levels of activated caspase 3
antigen in cortical neurons.