Formation of neurofibrillary tangles in P301L tau transgenic mice induced by A beta 42 fibrils

beta -Amyloid plaques and neurofibrillary tangles (NFTs) are the defining neuropathological hallmarks of Alzheimer's disease, but their pathophysiological relation is unclear. Injection of beta -amyloid A beta sub(42) fibrils into the brains of P301L mutant tau transgenic mice caused fivefold increases in the numbers of NFTs in cell bodies within the amygdala from where neurons project to the injection sites. Gallyas silver impregnation identified NFTs that contained tau phosphorylated at serine 212/threonine 214 and serine 422. NFTs were composed of twisted filaments and occurred in 6-month-old mice as early as 18 days after A beta sub(42) injections. Our data support the hypothesis that A beta sub(42) fibrils can accelerate NFT formation in vivo.