Size of neocortical neurons in control subjects and in Alzheimer's disease

Abstract

The aim of the present study was to estimate mean neuronal volume and absolute size distributions of the neocortical neurons in brains from controls and AD patients using stereological methods based on unbiased principles to determine whether changes in absolute cell size are part of the neuropathological pattern of Alzheimer's disease. The neocortex of 8 patients with Alzheimer's disease (AD), mean age 81·1 (68–94) y was compared with 9 nondemented controls, mean age 80·9 (65–101) y. The brains came from Johns Hopkins University Hospital (JHUH) in Baltimore, USA, the Netherlands Brain Bank (NBB), and from a large brain repository in Denmark. The rotator method was used to obtain an estimate of cell volumes providing absolute size distributions of the volume of both cell perikaryon and cell nuclei. The geometric mean volume of cell nuclei in neocortical neurons was 328 μm³ (interindividual CV = 0·15) in the Alzheimer group compared with 277 μm³ (interindividual CV = 0·17) in controls which was a statistically significant increase (P = 0·049). The perikaryal volume was 1117 μm³ in the Alzheimer group compared with 999 μm³ in controls which was a nonsignificant difference (P = 0·20). There was a highly significant correlation between the nuclear and perikaryal volumes in all individuals. The average slope of the regression lines was significantly higher in the Alzheimer patients than in the controls, illustrating that nuclear hypertrophy was more pronounced in the largest neurons.