Frequency of stages of Alzheimer-related lesions in different age categories.

Alzheimer's disease is a relentlessly progressing dementing disorder. Major pathological hallmarks include extracellular deposits of amyloid protein and intraneuronal neurofibrillary changes. No remissions occur in the course of the disease. Initial amyloid deposits develop in poorly myelinated areas of the basal neocortex. From there, they spread into adjoining areas and the hippocampus. Deposits eventually infiltrate all cortical areas, including densely myelinated primary fields of the neocortex (stages A-C). Intraneuronal lesions develop initially in the transentorhinal region, then spread in a predictable manner across other areas (stages I-VI). At stages I-II, neurofibrillary changes develop preferentially in the absence of amyloid deposits. A proportion of cases shows early development of amyloid deposits and/or intraneuronal changes. Advanced age is thus not a prerequisite for the evolution of the lesions. Alzheimer's disease is an age-related, not an age-dependent disease. The degree of brain destruction at stages III-IV frequently leads to the appearance of initial clinical symptoms. The stages V-VI representing fully developed Alzheimer's disease are increasingly prevalent with increasing age. The arithmetic means of the stages of both the amyloid-depositing and the neurofibrillary pathology increase with age. Age is a risk factor for Alzheimer's disease.