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Neuropathological and behavioral features of an APP/PS1/MAPT (6xTg) transgenic model of Alzheimer’s disease
Alzheimer's disease is associated with various brain dysfunctions, including memory impairment, neuronal loss, astrocyte activation, amyloid-β plaques, and neurofibrillary tangles. Transgenic animal models of Alzheimer's disease have proven to be invaluable for the basic research of Alzhei...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9175339/ https://www.ncbi.nlm.nih.gov/pubmed/35676711 http://dx.doi.org/10.1186/s13041-022-00933-8 |
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author | Tag, Sung Hyun Kim, Baeksun Bae, Jinhee Chang, Keun-A Im, Heh-In |
author_facet | Tag, Sung Hyun Kim, Baeksun Bae, Jinhee Chang, Keun-A Im, Heh-In |
author_sort | Tag, Sung Hyun |
collection | PubMed |
description | Alzheimer's disease is associated with various brain dysfunctions, including memory impairment, neuronal loss, astrocyte activation, amyloid-β plaques, and neurofibrillary tangles. Transgenic animal models of Alzheimer's disease have proven to be invaluable for the basic research of Alzheimer's disease. However, Alzheimer's disease mouse models developed so far do not fully recapitulate the pathological and behavioral features reminiscent of Alzheimer's disease in humans. Here, we investigated the neurobehavioral sequelae in the novel 6xTg mouse model of Alzheimer's disease, which was developed by incorporating human tau containing P301L mutation in the widely used 5xFAD mouse model of Alzheimer's disease. At 11-months-old, 6xTg mice displayed the core pathological processes found in Alzheimer's disease, including accumulation of amyloid-β plaque, extensive neuronal loss, elevated level of astrocyte activation, and abnormal tau phosphorylation in the brain. At 9 to 11-months-old, 6xTg mice exhibited both cognitive and non-cognitive behavioral impairments relevant to Alzheimer’s disease, including memory loss, hyperlocomotion, anxiety-like behavior, depression-like behavior, and reduced sensorimotor gating. Our data suggest that the aged 6xTg mouse model of Alzheimer's disease presents pathological and cognitive-behavioral features reminiscent of Alzheimer's disease in humans. Thus, the 6xTg mouse model of Alzheimer's disease may be a valuable model for studying Alzheimer’s disease-relevant non-cognitive behaviors. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13041-022-00933-8. |
format | Online Article Text |
id | pubmed-9175339 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-91753392022-06-09 Neuropathological and behavioral features of an APP/PS1/MAPT (6xTg) transgenic model of Alzheimer’s disease Tag, Sung Hyun Kim, Baeksun Bae, Jinhee Chang, Keun-A Im, Heh-In Mol Brain Research Alzheimer's disease is associated with various brain dysfunctions, including memory impairment, neuronal loss, astrocyte activation, amyloid-β plaques, and neurofibrillary tangles. Transgenic animal models of Alzheimer's disease have proven to be invaluable for the basic research of Alzheimer's disease. However, Alzheimer's disease mouse models developed so far do not fully recapitulate the pathological and behavioral features reminiscent of Alzheimer's disease in humans. Here, we investigated the neurobehavioral sequelae in the novel 6xTg mouse model of Alzheimer's disease, which was developed by incorporating human tau containing P301L mutation in the widely used 5xFAD mouse model of Alzheimer's disease. At 11-months-old, 6xTg mice displayed the core pathological processes found in Alzheimer's disease, including accumulation of amyloid-β plaque, extensive neuronal loss, elevated level of astrocyte activation, and abnormal tau phosphorylation in the brain. At 9 to 11-months-old, 6xTg mice exhibited both cognitive and non-cognitive behavioral impairments relevant to Alzheimer’s disease, including memory loss, hyperlocomotion, anxiety-like behavior, depression-like behavior, and reduced sensorimotor gating. Our data suggest that the aged 6xTg mouse model of Alzheimer's disease presents pathological and cognitive-behavioral features reminiscent of Alzheimer's disease in humans. Thus, the 6xTg mouse model of Alzheimer's disease may be a valuable model for studying Alzheimer’s disease-relevant non-cognitive behaviors. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13041-022-00933-8. BioMed Central 2022-06-08 /pmc/articles/PMC9175339/ /pubmed/35676711 http://dx.doi.org/10.1186/s13041-022-00933-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Tag, Sung Hyun Kim, Baeksun Bae, Jinhee Chang, Keun-A Im, Heh-In Neuropathological and behavioral features of an APP/PS1/MAPT (6xTg) transgenic model of Alzheimer’s disease |
title | Neuropathological and behavioral features of an APP/PS1/MAPT (6xTg) transgenic model of Alzheimer’s disease |
title_full | Neuropathological and behavioral features of an APP/PS1/MAPT (6xTg) transgenic model of Alzheimer’s disease |
title_fullStr | Neuropathological and behavioral features of an APP/PS1/MAPT (6xTg) transgenic model of Alzheimer’s disease |
title_full_unstemmed | Neuropathological and behavioral features of an APP/PS1/MAPT (6xTg) transgenic model of Alzheimer’s disease |
title_short | Neuropathological and behavioral features of an APP/PS1/MAPT (6xTg) transgenic model of Alzheimer’s disease |
title_sort | neuropathological and behavioral features of an app/ps1/mapt (6xtg) transgenic model of alzheimer’s disease |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9175339/ https://www.ncbi.nlm.nih.gov/pubmed/35676711 http://dx.doi.org/10.1186/s13041-022-00933-8 |
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