The aim of the present study was to estimate mean neuronal volume and absol
ute size distributions of the neocortical neurons in brains from controls a
nd AD patients using stereological methods based on unbiased principles to
determine whether changes in absolute cell size are part of the neuropathol
ogical pattern of Alzheimer's disease. The neocortex of S patients with Alz
heimer's disease (PID), mean age 81.1 (68-94) y was compared with 9 nondeme
nted 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 distribu
tions of the volume of both cell perikaryon and cell nuclei. The geometric
mean volume of cell nuclei in neocortical neurons was 328 mum(3) (interindi
vidual CV = 0.15) in the Alzheimer group compared with 277 mum(3) (interind
ividual CV = 0.17) in controls which was a statistically significant increa
se (P = 0.049). The perikaryal volume was 1117 mum(3) in the Alzheimer grou
p compared with 999 mum(3) in controls which was a nonsignificant differenc
e (P = 0.2.0). There was a highly significant correlation between the nucle
ar and perikaryal volumes in ah individuals. The average slope of the regre
ssion lines was significantly higher in the Alzheimer patients than in the
controls, illustrating that nuclear hypertrophy was more pronounced in the
largest neurons.