Conservation of neuron number and size in entorhinal cortex layers II, III, and V/VI of aged primates.

Abstract

Past dogma asserted that extensive loss of cortical neurons accompanies normal aging. However, recent stereologic studies in humans, monkeys, and rodents have found little evidence of age-related neuronal loss in several cortical regions, including the neocortex and hippocampus. Yet to date, a complete investigation of age-related neuronal loss or size change has not been undertaken in the entorhinal cortex, a retrohippocampal structure essential for learning and memory. The aged rhesus macaque monkey (Macaca mulatta), a species that develops beta-amyloid plaques and exhibits cognitive deficits with age, is considered the best commonly available model of aging in humans. In the present study, we examined changes in total neuron number and size in layers II, III, and V/VI of the intermediate division of the entorhinal cortex in aged vs. nonaged rhesus monkeys by using unbiased stereologic methods. Total neuron number was conserved in aged primates when compared with nonaged adults in entorhinal cortex layer II (aged = 56,500 +/- 12,100, nonaged adult = 48,500 +/- 10,900; P = 0.37), layer III (aged = 205, 600 +/- 50,700, nonaged adult = 187,600 +/- 60,300; P = 0.66), and layers V/VI (aged = 246,400 +/- 76,700, nonaged adult = 236,800 +/- 69,600; P = 0.87). In each of the layers examined, neuronal area and volume were also conserved with aging. This lack of morphologically evident neurodegeneration in primate entorhinal cortex with aging further supports the concept that fundamental differences exist between the processes of normal "healthy" aging and pathologic age-related neurodegenerative disorders such as Alzheimer's disease.