Acetylcholinesterase-rich pyramidal neurons in the human association neocortex and hippocampal formation are virtually absent early in life, become established by adolescence, and appear to increase in density during adulthood and perhaps even senescence. Analogous neurons are not detectable in the adult monkey brain. This novel class of neurons may represent a uniquely human adaptation in primate evolution and may provide a neuroanatomical substrate for the mental development that occurs during the adult stages of life. These phylogenetically and ontogenetically progressive neurons are also markedly vulnerable to degeneration in Alzheimer's disease.