VOLUME AND NUMBER OF NEURONS OF THE HUMAN HIPPOCAMPAL-FORMATION IN NORMAL AGING AND ALZHEIMERS-DISEASE

In order to observe changes owing to aging and Alzheimer's disease (AD ) in the volumes of subdivisions of the hippocampus and the number of neurons of the hippocampal formation, 18 normal brains from subjects w ho died of nonneurological causes and had no history of long-term illn ess or dementia (ten of these brains comprised the aged control group) and 13 AD brains were analyzed. An optimized design for sampling, mea suring volume by using the Cavalieri principle, and counting the numbe r of neurons by using the optical disector was implemented on 50 mu m- thick cresyl-violet sections. The mean total volume of the principal s ubdivisions of the hippocampal formation (fascia dentata, hilus, CA3-2 , CA1, and subiculum) showed a negative correlation with age in normal subjects (r = -0.56, 2P < 0.05), and a 32% mean reduction in the AD g roup compared with controls (P < 0.001). This finding supports the mea surement of the coronal cross-sectional area and the volume of the hip pocampal formation in the clinical diagnosis of AD. There was an inver se relationship between the age of normal subjects and the number of n eurons in CA1 (r = -0.84, 2P < 0.0001) and subiculum (r = -0.49, 2P < 0.05) but not in other subdivisions. Pronounced AD-related reductions in neuron number were found only in the subiculum and the fascia denta ta. Compared with controls, both losses represented 23% of neurons (P < 0.05). These results 1) confirm that AD is a qualitatively different process from normal aging and 2) reveal the regional selectivity of n euron loss within the hippocampal formation in aging and AD, which may be relevant to understanding the mechanisms involved in the neuron lo ss associated with the two processes. (C) 1997 Wiley-Liss, Inc.