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A novel systems biology approach to evaluate mouse models of late-onset Alzheimer’s disease
BACKGROUND: Late-onset Alzheimer’s disease (LOAD) is the most common form of dementia worldwide. To date, animal models of Alzheimer’s have focused on rare familial mutations, due to a lack of frank neuropathology from models based on common disease genes. Recent multi-cohort studies of postmortem h...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656729/ https://www.ncbi.nlm.nih.gov/pubmed/33172468 http://dx.doi.org/10.1186/s13024-020-00412-5 |
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author | Preuss, Christoph Pandey, Ravi Piazza, Erin Fine, Alexander Uyar, Asli Perumal, Thanneer Garceau, Dylan Kotredes, Kevin P. Williams, Harriet Mangravite, Lara M. Lamb, Bruce T. Oblak, Adrian L. Howell, Gareth R. Sasner, Michael Logsdon, Benjamin A. Carter, Gregory W. |
author_facet | Preuss, Christoph Pandey, Ravi Piazza, Erin Fine, Alexander Uyar, Asli Perumal, Thanneer Garceau, Dylan Kotredes, Kevin P. Williams, Harriet Mangravite, Lara M. Lamb, Bruce T. Oblak, Adrian L. Howell, Gareth R. Sasner, Michael Logsdon, Benjamin A. Carter, Gregory W. |
author_sort | Preuss, Christoph |
collection | PubMed |
description | BACKGROUND: Late-onset Alzheimer’s disease (LOAD) is the most common form of dementia worldwide. To date, animal models of Alzheimer’s have focused on rare familial mutations, due to a lack of frank neuropathology from models based on common disease genes. Recent multi-cohort studies of postmortem human brain transcriptomes have identified a set of 30 gene co-expression modules associated with LOAD, providing a molecular catalog of relevant endophenotypes. RESULTS: This resource enables precise gene-based alignment between new animal models and human molecular signatures of disease. Here, we describe a new resource to efficiently screen mouse models for LOAD relevance. A new NanoString nCounter® Mouse AD panel was designed to correlate key human disease processes and pathways with mRNA from mouse brains. Analysis of the 5xFAD mouse, a widely used amyloid pathology model, and three mouse models based on LOAD genetics carrying APOE4 and TREM2*R47H alleles demonstrated overlaps with distinct human AD modules that, in turn, were functionally enriched in key disease-associated pathways. Comprehensive comparison with full transcriptome data from same-sample RNA-Seq showed strong correlation between gene expression changes independent of experimental platform. CONCLUSIONS: Taken together, we show that the nCounter Mouse AD panel offers a rapid, cost-effective and highly reproducible approach to assess disease relevance of potential LOAD mouse models. SUPPLEMENTARY INFORMATION: Supplementary information accompanies this paper at 10.1186/s13024-020-00412-5. |
format | Online Article Text |
id | pubmed-7656729 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-76567292020-11-13 A novel systems biology approach to evaluate mouse models of late-onset Alzheimer’s disease Preuss, Christoph Pandey, Ravi Piazza, Erin Fine, Alexander Uyar, Asli Perumal, Thanneer Garceau, Dylan Kotredes, Kevin P. Williams, Harriet Mangravite, Lara M. Lamb, Bruce T. Oblak, Adrian L. Howell, Gareth R. Sasner, Michael Logsdon, Benjamin A. Carter, Gregory W. Mol Neurodegener Methodology BACKGROUND: Late-onset Alzheimer’s disease (LOAD) is the most common form of dementia worldwide. To date, animal models of Alzheimer’s have focused on rare familial mutations, due to a lack of frank neuropathology from models based on common disease genes. Recent multi-cohort studies of postmortem human brain transcriptomes have identified a set of 30 gene co-expression modules associated with LOAD, providing a molecular catalog of relevant endophenotypes. RESULTS: This resource enables precise gene-based alignment between new animal models and human molecular signatures of disease. Here, we describe a new resource to efficiently screen mouse models for LOAD relevance. A new NanoString nCounter® Mouse AD panel was designed to correlate key human disease processes and pathways with mRNA from mouse brains. Analysis of the 5xFAD mouse, a widely used amyloid pathology model, and three mouse models based on LOAD genetics carrying APOE4 and TREM2*R47H alleles demonstrated overlaps with distinct human AD modules that, in turn, were functionally enriched in key disease-associated pathways. Comprehensive comparison with full transcriptome data from same-sample RNA-Seq showed strong correlation between gene expression changes independent of experimental platform. CONCLUSIONS: Taken together, we show that the nCounter Mouse AD panel offers a rapid, cost-effective and highly reproducible approach to assess disease relevance of potential LOAD mouse models. SUPPLEMENTARY INFORMATION: Supplementary information accompanies this paper at 10.1186/s13024-020-00412-5. BioMed Central 2020-11-10 /pmc/articles/PMC7656729/ /pubmed/33172468 http://dx.doi.org/10.1186/s13024-020-00412-5 Text en © The Author(s) 2020 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/. The Creative Commons Public Domain Dedication waiver (http://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 | Methodology Preuss, Christoph Pandey, Ravi Piazza, Erin Fine, Alexander Uyar, Asli Perumal, Thanneer Garceau, Dylan Kotredes, Kevin P. Williams, Harriet Mangravite, Lara M. Lamb, Bruce T. Oblak, Adrian L. Howell, Gareth R. Sasner, Michael Logsdon, Benjamin A. Carter, Gregory W. A novel systems biology approach to evaluate mouse models of late-onset Alzheimer’s disease |
title | A novel systems biology approach to evaluate mouse models of late-onset Alzheimer’s disease |
title_full | A novel systems biology approach to evaluate mouse models of late-onset Alzheimer’s disease |
title_fullStr | A novel systems biology approach to evaluate mouse models of late-onset Alzheimer’s disease |
title_full_unstemmed | A novel systems biology approach to evaluate mouse models of late-onset Alzheimer’s disease |
title_short | A novel systems biology approach to evaluate mouse models of late-onset Alzheimer’s disease |
title_sort | novel systems biology approach to evaluate mouse models of late-onset alzheimer’s disease |
topic | Methodology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656729/ https://www.ncbi.nlm.nih.gov/pubmed/33172468 http://dx.doi.org/10.1186/s13024-020-00412-5 |
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