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A comprehensive multiomics approach toward understanding the relationship between aging and dementia
Because age is the greatest risk factor for sporadic Alzheimer's disease (AD), phenotypic screens based upon old age-associated brain toxicities were used to develop the potent neurotrophic drug J147. Since certain aspects of aging may be primary cause of AD, we hypothesized that J147 would be...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694064/ https://www.ncbi.nlm.nih.gov/pubmed/26564964 |
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author | Currais, Antonio Goldberg, Joshua Farrokhi, Catherine Chang, Max Prior, Marguerite Dargusch, Richard Daugherty, Daniel Armando, Aaron Quehenberger, Oswald Maher, Pamela Schubert, David |
author_facet | Currais, Antonio Goldberg, Joshua Farrokhi, Catherine Chang, Max Prior, Marguerite Dargusch, Richard Daugherty, Daniel Armando, Aaron Quehenberger, Oswald Maher, Pamela Schubert, David |
author_sort | Currais, Antonio |
collection | PubMed |
description | Because age is the greatest risk factor for sporadic Alzheimer's disease (AD), phenotypic screens based upon old age-associated brain toxicities were used to develop the potent neurotrophic drug J147. Since certain aspects of aging may be primary cause of AD, we hypothesized that J147 would be effective against AD-associated pathology in rapidly aging SAMP8 mice and could be used to identify some of the molecular contributions of aging to AD. An inclusive and integrative multiomics approach was used to investigate protein and gene expression, metabolite levels, and cognition in old and young SAMP8 mice. J147 reduced cognitive deficits in old SAMP8 mice, while restoring multiple molecular markers associated with human AD, vascular pathology, impaired synaptic function, and inflammation to those approaching the young phenotype. The extensive assays used in this study identified a subset of molecular changes associated with aging that may be necessary for the development of AD. |
format | Online Article Text |
id | pubmed-4694064 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-46940642016-01-07 A comprehensive multiomics approach toward understanding the relationship between aging and dementia Currais, Antonio Goldberg, Joshua Farrokhi, Catherine Chang, Max Prior, Marguerite Dargusch, Richard Daugherty, Daniel Armando, Aaron Quehenberger, Oswald Maher, Pamela Schubert, David Aging (Albany NY) Research Paper Because age is the greatest risk factor for sporadic Alzheimer's disease (AD), phenotypic screens based upon old age-associated brain toxicities were used to develop the potent neurotrophic drug J147. Since certain aspects of aging may be primary cause of AD, we hypothesized that J147 would be effective against AD-associated pathology in rapidly aging SAMP8 mice and could be used to identify some of the molecular contributions of aging to AD. An inclusive and integrative multiomics approach was used to investigate protein and gene expression, metabolite levels, and cognition in old and young SAMP8 mice. J147 reduced cognitive deficits in old SAMP8 mice, while restoring multiple molecular markers associated with human AD, vascular pathology, impaired synaptic function, and inflammation to those approaching the young phenotype. The extensive assays used in this study identified a subset of molecular changes associated with aging that may be necessary for the development of AD. Impact Journals LLC 2015-11-11 /pmc/articles/PMC4694064/ /pubmed/26564964 Text en Copyright: © 2015 Currais et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Currais, Antonio Goldberg, Joshua Farrokhi, Catherine Chang, Max Prior, Marguerite Dargusch, Richard Daugherty, Daniel Armando, Aaron Quehenberger, Oswald Maher, Pamela Schubert, David A comprehensive multiomics approach toward understanding the relationship between aging and dementia |
title | A comprehensive multiomics approach toward understanding the relationship between aging and dementia |
title_full | A comprehensive multiomics approach toward understanding the relationship between aging and dementia |
title_fullStr | A comprehensive multiomics approach toward understanding the relationship between aging and dementia |
title_full_unstemmed | A comprehensive multiomics approach toward understanding the relationship between aging and dementia |
title_short | A comprehensive multiomics approach toward understanding the relationship between aging and dementia |
title_sort | comprehensive multiomics approach toward understanding the relationship between aging and dementia |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694064/ https://www.ncbi.nlm.nih.gov/pubmed/26564964 |
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