Volume and number of neurons of the human hippocampal formation in normal aging and Alzheimer's disease

TLDR

The study examined how aging and Alzheimer’s disease affect hippocampal subdivision volumes and neuron counts using 18 normal and 13 AD postmortem brains. Researchers applied an optimized sampling protocol, measuring volumes with the Cavalieri principle and counting neurons with the optical disector on 50 µm cresyl‑violet sections. They found hippocampal volumes decline with age and are 32 % smaller in AD, neuron loss is age‑related in CA1 and subiculum but AD selectively reduces neurons in subiculum and fascia dentata by 23 %, confirming AD’s distinct, regionally selective neurodegeneration. © 1997 Wiley‑Liss, Inc.; J.

Abstract

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 who died of nonneurological causes and had no history of long-term illness or dementia (ten of these brains comprised the aged control group) and 13 AD brains were analyzed. An optimized design for sampling, measuring volume by using the Cavalieri principle, and counting the number of neurons by using the optical disector was implemented on 50 μm-thick cresyl-violet sections. The mean total volume of the principal subdivisions 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 group compared with controls (P < 0.001). This finding supports the measurement of the coronal cross-sectional area and the volume of the hippocampal formation in the clinical diagnosis of AD. There was an inverse relationship between the age of normal subjects and the number of neurons 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 dentata. 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 neuron loss within the hippocampal formation in aging and AD, which may be relevant to understanding the mechanisms involved in the neuron loss associated with the two processes. J. Comp. Neurol. 379:482–494, 1997. © 1997 Wiley-Liss, Inc.