Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease

Summary. The distinction between the neurodegenerative changes that accompany normal ageing and those that characterise Alzheimer's disease is not clear. The resolution of this issue has important implications for the design of therapeutic and investigative strategies. To this end we have used modern stereological techniques to compare the regional pattern of neuronal cell loss in the hippocampus related to normal ageing to that associated with Alzheimer's disease. The loss related to normal ageing was evaluated from estimates of the total number of neurons in each of the major hippocampal subdivisions of 45 normal ageing subjects who ranged in age from 13 to 101 years. The Alzheimer's disease related losses were evaluated from similar data obtained from 7 cases of Alzheimer's disease and 14 age matched controls. Qualitative differences were observed in the regional patterns of neuronal loss related to normal ageing and Alzheimer's disease. The most distinctive Alzheimer's disease related neuron loss was seen in the CA1 region of the hippocampus. In the normal ageing group there was almost no neuron loss in this region (final neuron count in the CA1 region: 4·40 X 10⁶ neurons for the Alzheimer's disease group vs 14·08 × 10⁶ neurons in the normal ageing group). It is concluded that the neurodegenerative processes associated with normal ageing and with Alzheimer's disease are qualitatively different and that Alzheimer's disease is not accelerated by ageing but is a distinct pathological process.