No global neocortical nerve cell loss in brains from patients with senile dementia of Alzheimer's type

Regeur, Lisbeth; Jensen, G; Pakkenberg, H.; Evans, Stephen M.; Pakkenberg, Bente

doi:10.1016/0197-4580(94)90030-2

Cited by 152 publications

(79 citation statements)

References 22 publications

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“…They reported the neuronal density in the frontal lobe to be 13364 neurons\mm$ in AD and 20754 neurons\mm$ in controls, in contrast to the present study in which the frontal lobe AD neuronal density of 42950 neurons\mm$ was similar to that of the controls, 40880 neurons\mm$. The neuronal density in this study is in accordance with previously reported plastic embedded numerical nerve cell densities for this age group (Regeur et al 1994) and surprisingly low in the Everall et al paper, especially taking into consideration that Everall et al used paraffin embedding. Apart from the different embedding media, different ways of identifying neurons and glial cells is a potential problem as neither of these 2 studies used specific cell markers.…”

Section: contrasting

confidence: 56%

“…This was also the case for the volume of archicortex (Regeur, 1999). One study based on stereological counting methods showed no global neocortical neuron loss (Regeur et al 1994), while profound neuronal loss in entorhinal cortex of AD patients and a significant neuron loss in the superior temporal sulcus region has been reported (Gomez-Isla et al 1996 ;Gomez-Isla et al 1997). Mann et al (1985), using measures of cell density and cell diameter in a nonisotropic design, reported a loss of pyramidal neurons and a decrease of the nucleolus volume in Alzheimer brains.…”

Section: mentioning

confidence: 99%

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

et al. 2001

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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.

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Section: contrasting

confidence: 56%

Section: mentioning

confidence: 99%

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

et al. 2001

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“…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).…”

Section: Discussionmentioning

confidence: 83%

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

et al. 2002

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APP23 transgenic mice express mutant human amyloid precursor protein and develop amyloid plaques predominantly in neocortex and hippocampus progressively with age, similar to Alzheimer's disease. We have previously reported neuron loss in the hippocampal CA1 region of 14-to 18-month-old APP23 mice. In contrast, no neuron loss was found in neocortex. In the present study we have reinvestigated neocortical neuron numbers in adult and aged APP23 mice. Surprisingly, results revealed that 8-month-old APP23 mice have 13 and 14% more neocortical neurons compared with 8-month-old wild-type and 27-month-old APP23 mice, respectively. In 27-month-old APP23 mice we found an inverse correlation between amyloid load and neuron number. These results suggest that APP23 mice have more neurons until they develop amyloid plaques but then lose neurons in the process of cerebral amyloidogenesis. Supporting this notion, we found more neurons with a necroticapoptotic phenotype in the neocortex of 24-month-old APP23 mice compared with age-matched wild-type mice. Stimulated by recent reports that demonstrated neurogenesis after targeted neuron death in the mouse neocortex, we have also examined neurogenesis in APP23 mice. Strikingly, we found a fourfold to sixfold increase in newly produced cells in 24-month-old APP23 mice compared with both age-matched wildtype mice and young APP23 transgenic mice. However, subsequent cellular phenotyping revealed that none of the newly generated cells in neocortex had a neuronal phenotype. The majority were microglial and to a lesser extent astroglial cells. We conclude that cerebral amyloidosis in APP23 mice causes a modest neuron loss in neocortex and induces marked gliogenesis.

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“…13 With similar assumption-free stereological techniques a selective neuronal loss has been demonstrated in the hippocampal CA1 field of AD patients while no general neuron loss could be detected in the neocortex. 14,15 Two other transgenic mouse models have been described to develop age-related cerebral A␤ deposition characteristic of AD. A four-to six-fold overexpression of APP mRNA and a more than 10-fold increase in APP was reported for the PDAPP mice.…”

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confidence: 99%