Alzheimer's disease and the aging brain.

The frequencies of each of the several types of dementia are enumerated, showing that Alzheimer's disease is present in about 80% of cases. Cerebral changes associated with cognitively normal aging include shrinkage of large cortical neurons but not a significant loss of total neuronal number. Nevertheless, the population density of synapses measured by confocal microscopy does decline significantly in normal aging. The classical lesions of Alzheimer's disease are neuritic plaques and neurofibrillary tangles, and their frequency correlates with declining cognitive measures. Although amyloid is prominent in plaques, it is probably not the agent of destruction. That role seems to be held by Abeta oligomers. The strongest structural correlate with cognitive tests is synapse loss, which is probably caused by Abeta oligopeptides in the terminal axons and dendrites.