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Intracellular Aβ triggers neuron loss in the cholinergic system of the APP/PS1KI mouse model of Alzheimer's disease.
Neurobiol Aging. 2010 Jul; 31(7):1153-63.NA

Abstract

Loss of cholinergic neurons in the Nucleus Basalis of Meynert in Alzheimer's disease (AD) patients was one of the first discoveries of neuron loss in AD. Despite an intense focus on the cholinergic system in AD, the reason for this cholinergic neuron loss is yet unknown. In the present study we examined Abeta-induced pathology and neuron loss in the cholinergic system of the bigenic APP/PS1KI mouse model. Expression of the APP transgene was found in ChAT-positive neurons of motor nuclei accompanied by robust intracellular Abeta accumulation, whereas no APP expressing neurons and thus no intracellular Abeta accumulation were found in neither the forebrain or pons complexes, nor in the caudate putamen. This expression pattern was used as a model system to study the effect of intra- and extracellular Abeta accumulation on neuron loss in the cholinergic system. Stereological quantification revealed a loss of ChAT-positive neurons in APP/PS1KI mice only in the motor nuclei Mo5 and 7N accumulating intracellular Abeta. This study supports the hypothesis of intracellular Abeta accumulation as an early pathological alteration contributing to cell death 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 Goettingen, Germany.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18771817

Citation

Christensen, Ditte Z., et al. "Intracellular Aβ Triggers Neuron Loss in the Cholinergic System of the APP/PS1KI Mouse Model of Alzheimer's Disease." Neurobiology of Aging, vol. 31, no. 7, 2010, pp. 1153-63.
Christensen DZ, Bayer TA, Wirths O. Intracellular Aβ triggers neuron loss in the cholinergic system of the APP/PS1KI mouse model of Alzheimer's disease. Neurobiol Aging. 2010;31(7):1153-63.
Christensen, D. Z., Bayer, T. A., & Wirths, O. (2010). Intracellular Aβ triggers neuron loss in the cholinergic system of the APP/PS1KI mouse model of Alzheimer's disease. Neurobiology of Aging, 31(7), 1153-63. https://doi.org/10.1016/j.neurobiolaging.2008.07.022
Christensen DZ, Bayer TA, Wirths O. Intracellular Aβ Triggers Neuron Loss in the Cholinergic System of the APP/PS1KI Mouse Model of Alzheimer's Disease. Neurobiol Aging. 2010;31(7):1153-63. PubMed PMID: 18771817.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intracellular Aβ triggers neuron loss in the cholinergic system of the APP/PS1KI mouse model of Alzheimer's disease. AU - Christensen,Ditte Z, AU - Bayer,Thomas A, AU - Wirths,Oliver, Y1 - 2008/09/03/ PY - 2008/03/27/received PY - 2008/07/24/revised PY - 2008/07/28/accepted PY - 2008/9/6/pubmed PY - 2010/12/14/medline PY - 2008/9/6/entrez SP - 1153 EP - 63 JF - Neurobiology of aging JO - Neurobiol. Aging VL - 31 IS - 7 N2 - Loss of cholinergic neurons in the Nucleus Basalis of Meynert in Alzheimer's disease (AD) patients was one of the first discoveries of neuron loss in AD. Despite an intense focus on the cholinergic system in AD, the reason for this cholinergic neuron loss is yet unknown. In the present study we examined Abeta-induced pathology and neuron loss in the cholinergic system of the bigenic APP/PS1KI mouse model. Expression of the APP transgene was found in ChAT-positive neurons of motor nuclei accompanied by robust intracellular Abeta accumulation, whereas no APP expressing neurons and thus no intracellular Abeta accumulation were found in neither the forebrain or pons complexes, nor in the caudate putamen. This expression pattern was used as a model system to study the effect of intra- and extracellular Abeta accumulation on neuron loss in the cholinergic system. Stereological quantification revealed a loss of ChAT-positive neurons in APP/PS1KI mice only in the motor nuclei Mo5 and 7N accumulating intracellular Abeta. This study supports the hypothesis of intracellular Abeta accumulation as an early pathological alteration contributing to cell death in AD. SN - 1558-1497 UR - https://www.unboundmedicine.com/medline/citation/18771817/Intracellular_Aβ_triggers_neuron_loss_in_the_cholinergic_system_of_the_APP/PS1KI_mouse_model_of_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-4580(08)00278-9 DB - PRIME DP - Unbound Medicine ER -