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 81n1 (68-94) y was compared with 9 nondemented controls, mean age 80n9 (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 µm$ (interindividual CV l 0n15) in the Alzheimer group compared with 277 µm$ (interindividual CV l 0n17) in controls which was a statistically significant increase (P l 0n049). The perikaryal volume was 1117 µm$ in the Alzheimer group compared with 999 µm$ in controls which was a nonsignificant difference (P l 0n20). 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.

Amyloid-Associated Neuron Loss and Gliogenesis in the Neocortex of Amyloid Precursor Protein Transgenic Mice

“…The neuron loss in neocortex of APP23 mice appears modest, but in fact exceeds the 2-6% global neuron loss reported in AD neocortex using similar stereological methodology (Regeur et al, 1994;Bundgaard et al, 2001). In contrast, 32% neuron loss has been reported in AD if the entorhinal cortex is analyzed separately, and up to 90% neuron loss was observed when individual laminae of the entorhinal cortex were analyzed, emphasizing that the neuropathic manifestations of AD are region-specific (Gomez-Isla et al, 1996a).…”

Progressive degeneration of nonphosphorylated neurofilament protein‐enriched pyramidal neurons predicts cognitive impairment in Alzheimer's disease: Stereologic analysis of prefrontal cortex area 9

“…However, it is not possible to assess the degree of effective viability of these cells from the present study. Clearly, these neurons are undergoing intracellular trafficking alterations and are known to show signs of abnormal metabolism (Dayan and Ball, 1973), nuclear pathology (Bundgaard et al, 2001), as well as sequestration of a variety of RNA species within NFT (Ginsberg et al, 1997(Ginsberg et al, , 1998. Elucidation of the molecular bases of the selective vulnerability of SMI-32-immunoreactive neurons will ultimately require comparative analyses with other pyramidal cells using approaches such as laser-guided microcapture and differential display.…”

Mitochondrial Function and Cell Size: An Allometric Relationship

“…The age-dependent decline in mitochondrial activity could, in theory, be partly due to the underlying cell size increase. Similarly to aging, many diseases, like Alzheimer disease and type II 30 diabetes, which are well-known to display decreased mitochondrial activity, are also characterised by cellular hypertrophy [41][42][43]. Possible causalities between cell size and mitochondrial activity should be investigated further in these settings.…”