This article reviews the possible relationships between the localization of cellular pathologic changes in Alzheimer's disease (AD), and the distribution of neuronal components of the neocortical circuitry that are affected by these alterations. In particular, evidence from the study of large autopsy series supporting the role of the inferior temporal cortex as a key area in the progression of the dementing process is presented. The notion of selective vulnerability in AD at the level of affected neocortical association areas, layers, and specific cell populations is discussed to provide insight into the molecular background of the development of neurofibrillary tangles within the cerebral cortex. Moreover, recent data on pathological correlates of apraxia in AD are examined in the light of the hypothesis of global corticocortical disconnection in this disorder.