Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP

JNPL3 transgenic mice expressing a mutant tau protein, which develop neurofibrillary tangles and progressive motor disturbance, were crossed with Tg2576 transgenic mice expressing mutant beta -amyloid precursor protein (APP), thus modulating the APP-A beta (beta -amyloid peptide) environment. The resulting double mutant (tau/APP) progeny and the Tg2576 parental strain developed A beta deposits at the same age; however, relative to JNPL3 mice, the double mutants exhibited neurofibrillary tangle pathology that was substantially enhanced in the limbic system and olfactory cortex. These results indicate that either APP or A beta influences the formation of neurofibrillary tangles. The interaction between A beta and tau pathologies in these mice supports the hypothesis that a similar interaction occurs in Alzheimer's disease.