Alzheimer s disease is a neurodegenerative disorder characterized neuropathologically by beta amyloid plaques, neurofibrillary tangles, gliosis and neuronal loss. Recently, we have elucidated a molecular cascade of cell death induced by A beta 25 35 involving the activation of nuclear factor kappa B (NF kB), p53, and c Jun transcription factors in vitro. At present, no comparative reports have been published to establish a similar cell death signalization pathway in in vitro and in in vivo. The aim of this investigation was to determine if AD brains might activate NF kB, p53, c Jun, Par 4 transcription factors and to establish whether there exist a relationship between neuronal DNA damage and transcription factors activation.We investigated Ab plaques, neurofibrillary tangles and NF kB, p53, and c Jun transcription factor activation in five cerebral regions from 3 normal subjects and from six demented patient with sporadic AD and one patient with AD familiar according to CERAD criteria. Using TUNEL we determine neuronal damage.We demonstrated neuronal damage in 17 out of 50 regions evaluated as TUNEL positive, and their distribution was heterogeneous in all brain regions evaluated; and the activation of NF kB, p53, c Jun and Par 4 transcription factors from case # 24 and #22, corresponding to TUNEL positive.We found a correlation between severity of DNA damage and nuclear activation of the transcription factors. These findings suggest that the AD brain may induce cell death by a molecular signalization similar to a non neuronal model by Ab exposure. This in situ study might validate previous Ab induced cell death observations in vitro.