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Recent research indicates that apoptotic mechanisms may be involved in cell death in Alzheimer's disease (AD). We studied the expression of three members of the Bcl-2 protein family, Bcl-2, Bcl-x, and Bax, in a selection of senile and DS-related AD patients as well as in controls. These proteins are all associated with apoptotic mechanisms. In contrast to previous reports, neuronal Bcl-2 labeling was not detected in our cases, although there was some weak and inconsistent glial cell labeling. Neuronal Bcl-x expression was virtually absent in controls and the presence of the protein in AD patients was neither consistent nor specific. Some reactive glial cells were strongly labeled with the Bcl-x antibody. In contrast Bax, a protein that is believed to promote apoptosis, was widely expressed by neurones but was mainly present in areas other than CA1 in the hippocampus. Neuritic elements of some senile plaques were clearly and strongly labeled with this antibody, whereas neurofibrillary tangles and neuropil threads were not. Double labeling studies indicated that AT8-positive cells and neurites were never Bax-positive and vice versa. The possible implications of the different expression patterns are discussed in relation to neurone death in AD.