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Deciphering the Molecular Profile of Plaques, Memory Decline and Neuron Loss in Two Mouse Models for Alzheimer’s Disease by Deep Sequencing

One of the central research questions on the etiology of Alzheimer’s disease (AD) is the elucidation of the molecular signatures triggered by the amyloid cascade of pathological events. Next-generation sequencing allows the identification of genes involved in disease processes in an unbiased manner....

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Autores principales: Bouter, Yvonne, Kacprowski, Tim, Weissmann, Robert, Dietrich, Katharina, Borgers, Henning, Brauß, Andreas, Sperling, Christian, Wirths, Oliver, Albrecht, Mario, Jensen, Lars R., Kuss, Andreas W., Bayer, Thomas A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997018/
https://www.ncbi.nlm.nih.gov/pubmed/24795628
http://dx.doi.org/10.3389/fnagi.2014.00075
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author Bouter, Yvonne
Kacprowski, Tim
Weissmann, Robert
Dietrich, Katharina
Borgers, Henning
Brauß, Andreas
Sperling, Christian
Wirths, Oliver
Albrecht, Mario
Jensen, Lars R.
Kuss, Andreas W.
Bayer, Thomas A.
author_facet Bouter, Yvonne
Kacprowski, Tim
Weissmann, Robert
Dietrich, Katharina
Borgers, Henning
Brauß, Andreas
Sperling, Christian
Wirths, Oliver
Albrecht, Mario
Jensen, Lars R.
Kuss, Andreas W.
Bayer, Thomas A.
author_sort Bouter, Yvonne
collection PubMed
description One of the central research questions on the etiology of Alzheimer’s disease (AD) is the elucidation of the molecular signatures triggered by the amyloid cascade of pathological events. Next-generation sequencing allows the identification of genes involved in disease processes in an unbiased manner. We have combined this technique with the analysis of two AD mouse models: (1) The 5XFAD model develops early plaque formation, intraneuronal Aβ aggregation, neuron loss, and behavioral deficits. (2) The Tg4–42 model expresses N-truncated Aβ(4–42) and develops neuron loss and behavioral deficits albeit without plaque formation. Our results show that learning and memory deficits in the Morris water maze and fear conditioning tasks in Tg4–42 mice at 12 months of age are similar to the deficits in 5XFAD animals. This suggested that comparative gene expression analysis between the models would allow the dissection of plaque-related and -unrelated disease relevant factors. Using deep sequencing differentially expressed genes (DEGs) were identified and subsequently verified by quantitative PCR. Nineteen DEGs were identified in pre-symptomatic young 5XFAD mice, and none in young Tg4–42 mice. In the aged cohort, 131 DEGs were found in 5XFAD and 56 DEGs in Tg4–42 mice. Many of the DEGs specific to the 5XFAD model belong to neuroinflammatory processes typically associated with plaques. Interestingly, 36 DEGs were identified in both mouse models indicating common disease pathways associated with behavioral deficits and neuron loss.
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spelling pubmed-39970182014-05-02 Deciphering the Molecular Profile of Plaques, Memory Decline and Neuron Loss in Two Mouse Models for Alzheimer’s Disease by Deep Sequencing Bouter, Yvonne Kacprowski, Tim Weissmann, Robert Dietrich, Katharina Borgers, Henning Brauß, Andreas Sperling, Christian Wirths, Oliver Albrecht, Mario Jensen, Lars R. Kuss, Andreas W. Bayer, Thomas A. Front Aging Neurosci Neuroscience One of the central research questions on the etiology of Alzheimer’s disease (AD) is the elucidation of the molecular signatures triggered by the amyloid cascade of pathological events. Next-generation sequencing allows the identification of genes involved in disease processes in an unbiased manner. We have combined this technique with the analysis of two AD mouse models: (1) The 5XFAD model develops early plaque formation, intraneuronal Aβ aggregation, neuron loss, and behavioral deficits. (2) The Tg4–42 model expresses N-truncated Aβ(4–42) and develops neuron loss and behavioral deficits albeit without plaque formation. Our results show that learning and memory deficits in the Morris water maze and fear conditioning tasks in Tg4–42 mice at 12 months of age are similar to the deficits in 5XFAD animals. This suggested that comparative gene expression analysis between the models would allow the dissection of plaque-related and -unrelated disease relevant factors. Using deep sequencing differentially expressed genes (DEGs) were identified and subsequently verified by quantitative PCR. Nineteen DEGs were identified in pre-symptomatic young 5XFAD mice, and none in young Tg4–42 mice. In the aged cohort, 131 DEGs were found in 5XFAD and 56 DEGs in Tg4–42 mice. Many of the DEGs specific to the 5XFAD model belong to neuroinflammatory processes typically associated with plaques. Interestingly, 36 DEGs were identified in both mouse models indicating common disease pathways associated with behavioral deficits and neuron loss. Frontiers Media S.A. 2014-04-16 /pmc/articles/PMC3997018/ /pubmed/24795628 http://dx.doi.org/10.3389/fnagi.2014.00075 Text en Copyright © 2014 Bouter, Kacprowski, Weissmann, Dietrich, Borgers, Brauß, Sperling, Wirths, Albrecht, Jensen, Kuss and Bayer. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Bouter, Yvonne
Kacprowski, Tim
Weissmann, Robert
Dietrich, Katharina
Borgers, Henning
Brauß, Andreas
Sperling, Christian
Wirths, Oliver
Albrecht, Mario
Jensen, Lars R.
Kuss, Andreas W.
Bayer, Thomas A.
Deciphering the Molecular Profile of Plaques, Memory Decline and Neuron Loss in Two Mouse Models for Alzheimer’s Disease by Deep Sequencing
title Deciphering the Molecular Profile of Plaques, Memory Decline and Neuron Loss in Two Mouse Models for Alzheimer’s Disease by Deep Sequencing
title_full Deciphering the Molecular Profile of Plaques, Memory Decline and Neuron Loss in Two Mouse Models for Alzheimer’s Disease by Deep Sequencing
title_fullStr Deciphering the Molecular Profile of Plaques, Memory Decline and Neuron Loss in Two Mouse Models for Alzheimer’s Disease by Deep Sequencing
title_full_unstemmed Deciphering the Molecular Profile of Plaques, Memory Decline and Neuron Loss in Two Mouse Models for Alzheimer’s Disease by Deep Sequencing
title_short Deciphering the Molecular Profile of Plaques, Memory Decline and Neuron Loss in Two Mouse Models for Alzheimer’s Disease by Deep Sequencing
title_sort deciphering the molecular profile of plaques, memory decline and neuron loss in two mouse models for alzheimer’s disease by deep sequencing
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997018/
https://www.ncbi.nlm.nih.gov/pubmed/24795628
http://dx.doi.org/10.3389/fnagi.2014.00075
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