Intraneuronal neurofibrillary changes and extracellular A beta-amyloid deposits are neuropathologic hallmarks of Alzheimer's disease. Examination of numerous non-selected autopsy cases demonstrates that they are by no means normal concomitants of brain aging. Rather, the initial neurofibrillary changes indicate the beginning of Alzheimer's disease. A small proportion of cases displays particularly early development of the intraneuronal changes, indicating that advanced age is not a prerequisite for the evolution of the lesions. However, the mean of stages in the development of the specific neurofibrillary pathology increases with age. Alzheimer's disease is thus an age-related, not an age-dependent disease.