OBJECTIVES: To explore the mechanisms of neuronal loss and apoptosis in the brains of Alzheimer's disease (AD) patients, through studying the expression of proteins related to signal transduction pathways, which are important for neuron survival. METHODS: (1) Immunohistochemistry: Sections were double stained with Tunel and NSE antibodies. (2) The hippocampal tissue taken from 6 cases of AD and 6 cases of non-AD brains was homogenized. Protein estimation was done by Lowry method. Equal amounts of protein were taken from each specimen and immunoprecipitation was performed and analyzed by Western blot; color development was done by alkaline phosphatase method or luminol reagent. RESULTS: (1) Tunel positive neurons were found in both AD and non-AD brains, but the number in the former was more than the latter. (2) The AD hippocampal tissue showed diminished expression of Akt/PKB, CREB, P-CREB, increased expression of apoptosis-related protein apoptosis-inducing factor, and diminished expression of apoptosis-related protein bcl-2. The expression of bax did not change. CONCLUSIONS: Diminished expression of CREB, P-CREB, bcl-2 in AD hippocampus indicates that the neuron survival signal transduction pathway in AD brains is impaired. Neurons are in apoptotic or pro-apoptotic state. In addition, increased expression of apoptosis-inducing factor, diminished expression of bcl-2, which is an anti-apoptotic factor, promotes further neuron apoptosis.