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Brain transcriptomes of zebrafish and mouse Alzheimer's disease knock-in models imply early disrupted energy metabolism
Energy production is the most fundamentally important cellular activity supporting all other functions, particularly in highly active organs, such as brains. Here, we summarise transcriptome analyses of young adult (pre-disease) brains from a collection of 11 early-onset familial Alzheimer's di...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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The Company of Biologists Ltd
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8807579/ https://www.ncbi.nlm.nih.gov/pubmed/34842276 http://dx.doi.org/10.1242/dmm.049187 |
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author | Barthelson, Karissa Newman, Morgan Lardelli, Michael |
author_facet | Barthelson, Karissa Newman, Morgan Lardelli, Michael |
author_sort | Barthelson, Karissa |
collection | PubMed |
description | Energy production is the most fundamentally important cellular activity supporting all other functions, particularly in highly active organs, such as brains. Here, we summarise transcriptome analyses of young adult (pre-disease) brains from a collection of 11 early-onset familial Alzheimer's disease (EOFAD)-like and non-EOFAD-like mutations in three zebrafish genes. The one cellular activity consistently predicted as affected by only the EOFAD-like mutations is oxidative phosphorylation, which produces most of the energy of the brain. All the mutations were predicted to affect protein synthesis. We extended our analysis to knock-in mouse models of APOE alleles and found the same effect for the late onset Alzheimer's disease risk allele ε4. Our results support a common molecular basis for the initiation of the pathological processes leading to both early and late onset forms of Alzheimer's disease, and illustrate the utility of zebrafish and knock-in single EOFAD mutation models for understanding the causes of this disease. |
format | Online Article Text |
id | pubmed-8807579 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-88075792022-02-02 Brain transcriptomes of zebrafish and mouse Alzheimer's disease knock-in models imply early disrupted energy metabolism Barthelson, Karissa Newman, Morgan Lardelli, Michael Dis Model Mech Research Article Energy production is the most fundamentally important cellular activity supporting all other functions, particularly in highly active organs, such as brains. Here, we summarise transcriptome analyses of young adult (pre-disease) brains from a collection of 11 early-onset familial Alzheimer's disease (EOFAD)-like and non-EOFAD-like mutations in three zebrafish genes. The one cellular activity consistently predicted as affected by only the EOFAD-like mutations is oxidative phosphorylation, which produces most of the energy of the brain. All the mutations were predicted to affect protein synthesis. We extended our analysis to knock-in mouse models of APOE alleles and found the same effect for the late onset Alzheimer's disease risk allele ε4. Our results support a common molecular basis for the initiation of the pathological processes leading to both early and late onset forms of Alzheimer's disease, and illustrate the utility of zebrafish and knock-in single EOFAD mutation models for understanding the causes of this disease. The Company of Biologists Ltd 2022-01-26 /pmc/articles/PMC8807579/ /pubmed/34842276 http://dx.doi.org/10.1242/dmm.049187 Text en © 2022. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Barthelson, Karissa Newman, Morgan Lardelli, Michael Brain transcriptomes of zebrafish and mouse Alzheimer's disease knock-in models imply early disrupted energy metabolism |
title | Brain transcriptomes of zebrafish and mouse Alzheimer's disease knock-in models imply early disrupted energy metabolism |
title_full | Brain transcriptomes of zebrafish and mouse Alzheimer's disease knock-in models imply early disrupted energy metabolism |
title_fullStr | Brain transcriptomes of zebrafish and mouse Alzheimer's disease knock-in models imply early disrupted energy metabolism |
title_full_unstemmed | Brain transcriptomes of zebrafish and mouse Alzheimer's disease knock-in models imply early disrupted energy metabolism |
title_short | Brain transcriptomes of zebrafish and mouse Alzheimer's disease knock-in models imply early disrupted energy metabolism |
title_sort | brain transcriptomes of zebrafish and mouse alzheimer's disease knock-in models imply early disrupted energy metabolism |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8807579/ https://www.ncbi.nlm.nih.gov/pubmed/34842276 http://dx.doi.org/10.1242/dmm.049187 |
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