Transient intraneuronal A beta rather than extracellular plaque pathology correlates with neuron loss in the frontal cortex of APP/PS1KI mice
2008 | journal article. A publication with affiliation to the University of Göttingen.
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Transient intraneuronal A beta rather than extracellular plaque pathology correlates with neuron loss in the frontal cortex of APP/PS1KI mice
Christensen, D. Z.; Kraus, S. L.; Flohr, A.; Cotel, M.-C.; Wirths, O. & Bayer, T. A. (2008)
Acta Neuropathologica, 116(6) pp. 647-655. DOI: https://doi.org/10.1007/s00401-008-0451-6
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- Authors
- Christensen, Ditte Zerlang; Kraus, Sophie Luise; Flohr, Antonius; Cotel, Marie-Caroline; Wirths, Oliver; Bayer, Thomas A.
- Abstract
- The accumulation of beta-amyloid (A beta) plaques and neurofibrillary tangles consisting of hyperphosphorylated tau protein are pathological features of Alzheimer's disease (AD) commonly modeled in mice using known human familial mutations; however, the loss of neurons also found to occur in AD is rarely observed in such models. The mechanism of neuron degeneration remains unclear but is of great interest as it is very likely an important factor for the onset of adverse memory deficits occurring in individuals with AD. The role of A beta in the neuronal degeneration is a matter of controversial debates. In the present study we investigated the impact of extracellular plaque A beta versus intraneuronal A beta on neuronal cell death. The thalamus and the frontal cortex of the APP/PS1KI mouse model were chosen for stereological quantification representing regions with plaques only (thalamus) or plaques as well as intraneuronal A beta (frontal cortex). A loss of neurons was found in the frontal cortex at the age of 6 months coinciding with the decrease of intraneuronal immunoreactivity, suggesting that the neurons with early intraneuronal A beta accumulation were lost. Strikingly, no neuron loss was observed in the thalamus despite the development of abundant plaque pathology with levels comparable to the frontal cortex. This study suggests that plaques have no effect on neuron death whereas accumulation of intraneuronal A beta may be an early transient pathological event leading to neuron loss in AD.
- Issue Date
- 2008
- Status
- published
- Publisher
- Springer
- Journal
- Acta Neuropathologica
- ISSN
- 0001-6322