Mutant and native human β-amyloid precursor proteins in transgenic mouse brain

Human β-amyloid precursor protein (βAPP) has been targeted to transgenic neurons using synapsin I promoter-based chimeric transgenes. Native human βAPP was introduced as well as βAPP containing mutations genetically linked to familial Alzheimerʹs disease (AD) and to hereditary cerebral hemorrhage with amyloidosis-Dutch type. In mouse brain, human βAPP RNA was up to 60% as abundant as total endogenous βAPP RNA. Human βAPP gene expression was most abundant in the CA subfields of the hippocampus and in the piriform cortex. Correct processing of human βAPP at the β-secretase cleavage site was demonstrated in transgenic mouse brains. Despite a 40% increase in total βAPP immunoreactivity in lines expressing mutant human βAPP, no evidence of amyloid deposition was found in brains of mice up to 14 months in age. Higher levels of mutant human βAPP, increased age, or other factors may be necessary to elicit β-amyloid-related neuropathologies in the rodent brain.