Neuronal degeneration linked to apoptosis can be inhibited by a family of proteins known as inhibitors of apoptosis proteins (IAPs). We examined three members of the IAP family that are implicated in the regulation of neuronal death. We assessed NAIP, XIAP, and cIAP-2 protein levels in the entorhinal cortex of non-demented, cognitively impaired and Alzheimer's disease cases. Levels of paired helical filament-1 (PHF-1), a marker of neurofibrillary tangles, were assessed to determine their relationship to IAP levels. NAIP was decreased in AD cases compared to mildly impaired and unimpaired cases, and this decrease was associated with increased PHF-1 levels. Low NAIP levels were associated with higher Braak and Braak tangle stage and cognitive dysfunction. XIAP levels were higher in AD cases and cIAP-2 levels did not vary with clinical status. Our data suggest that decreased NAIP may place neurons at risk for the development of tangles and apoptosis.