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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.
Acta Neuropathol. 2008 Dec; 116(6):647-55.AN

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.

Authors+Show Affiliations

Division of Molecular Psychiatry and Alzheimer Ph.D. Graduate School, Department of Psychiatry, University of Goettingen, von-Siebold-Str. 5, 37075, Göttingen, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18974993

Citation

Christensen, Ditte Zerlang, et al. "Transient Intraneuronal a Beta Rather Than Extracellular Plaque Pathology Correlates With Neuron Loss in the Frontal Cortex of APP/PS1KI Mice." Acta Neuropathologica, vol. 116, no. 6, 2008, pp. 647-55.
Christensen DZ, Kraus SL, Flohr A, et al. Transient intraneuronal A beta rather than extracellular plaque pathology correlates with neuron loss in the frontal cortex of APP/PS1KI mice. Acta Neuropathol. 2008;116(6):647-55.
Christensen, D. Z., Kraus, S. L., Flohr, A., Cotel, M. C., Wirths, O., & Bayer, T. A. (2008). Transient intraneuronal A beta rather than extracellular plaque pathology correlates with neuron loss in the frontal cortex of APP/PS1KI mice. Acta Neuropathologica, 116(6), 647-55. https://doi.org/10.1007/s00401-008-0451-6
Christensen DZ, et al. Transient Intraneuronal a Beta Rather Than Extracellular Plaque Pathology Correlates With Neuron Loss in the Frontal Cortex of APP/PS1KI Mice. Acta Neuropathol. 2008;116(6):647-55. PubMed PMID: 18974993.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transient intraneuronal A beta rather than extracellular plaque pathology correlates with neuron loss in the frontal cortex of APP/PS1KI mice. AU - Christensen,Ditte Zerlang, AU - Kraus,Sophie Luise, AU - Flohr,Antonius, AU - Cotel,Marie-Caroline, AU - Wirths,Oliver, AU - Bayer,Thomas A, Y1 - 2008/10/31/ PY - 2008/10/01/received PY - 2008/10/22/accepted PY - 2008/10/22/revised PY - 2008/11/1/pubmed PY - 2009/2/4/medline PY - 2008/11/1/entrez SP - 647 EP - 55 JF - Acta neuropathologica JO - Acta Neuropathol. VL - 116 IS - 6 N2 - 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. SN - 1432-0533 UR - https://www.unboundmedicine.com/medline/citation/18974993/Transient_intraneuronal_A_beta_rather_than_extracellular_plaque_pathology_correlates_with_neuron_loss_in_the_frontal_cortex_of_APP/PS1KI_mice_ L2 - https://dx.doi.org/10.1007/s00401-008-0451-6 DB - PRIME DP - Unbound Medicine ER -