Enhanced neurofibrillary degeneration in transgenic mice expressing mutanttau and APP

JNPL3 transgenic mice expressing a mutant tau protein, which develop neurof ibrillary tangles and progressive motor disturbance, were crossed with Tg25 76 transgenic mice expressing mutant beta -amyloid precursor protein (APP), thus modulating the APP-A beta (beta -amyloid peptide) environment. The re sulting double mutant (tau/APP) progeny and the Tg2576 parental strain deve loped A beta deposits at the same age; however, relative to JNPL3 mice, the double mutants exhibited neurofibrillary tangle pathology that was substan tially enhanced in the limbic system and olfactory cortex. These results in dicate that either APP or A beta influences the formation of neurofibrillar y tangles. The interaction between A beta and tau pathologies in these mice supports the hypothesis that a similar interaction occurs in Alzheimer's d isease.