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Rhesus monkeys as a translational model for late‐onset Alzheimer's disease
Age is a major risk factor for late‐onset Alzheimer's disease (AD) but seldom features in laboratory models of the disease. Furthermore, heterogeneity in size and density of AD plaques observed in individuals are not recapitulated in transgenic mouse models, presenting an incomplete picture. We...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208787/ https://www.ncbi.nlm.nih.gov/pubmed/33951283 http://dx.doi.org/10.1111/acel.13374 |
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author | Souder, Dylan C. Dreischmeier, Isabelle A. Smith, Alex B. Wright, Samantha Martin, Stephen A. Sagar, Md Abdul Kader Eliceiri, Kevin W. Salamat, Shahriar M. Bendlin, Barbara B. Colman, Ricki J. Beasley, T. Mark Anderson, Rozalyn M. |
author_facet | Souder, Dylan C. Dreischmeier, Isabelle A. Smith, Alex B. Wright, Samantha Martin, Stephen A. Sagar, Md Abdul Kader Eliceiri, Kevin W. Salamat, Shahriar M. Bendlin, Barbara B. Colman, Ricki J. Beasley, T. Mark Anderson, Rozalyn M. |
author_sort | Souder, Dylan C. |
collection | PubMed |
description | Age is a major risk factor for late‐onset Alzheimer's disease (AD) but seldom features in laboratory models of the disease. Furthermore, heterogeneity in size and density of AD plaques observed in individuals are not recapitulated in transgenic mouse models, presenting an incomplete picture. We show that the amyloid plaque microenvironment is not equivalent between rodent and primate species, and that differences in the impact of AD pathology on local metabolism and inflammation might explain established differences in neurodegeneration and functional decline. Using brain tissue from transgenic APP/PSEN1 mice, rhesus monkeys with age‐related amyloid plaques, and human subjects with confirmed AD, we report altered energetics in the plaque microenvironment. Metabolic features included changes in mitochondrial distribution and enzymatic activity, and changes in redox cofactors NAD(P)H that were shared among species. A greater burden of lipofuscin was detected in the brains from monkeys and humans of advanced age compared to transgenic mice. Local inflammatory signatures indexed by astrogliosis and microglial activation were detected in each species; however, the inflamed zone was considerably larger for monkeys and humans. These data demonstrate the advantage of nonhuman primates in modeling the plaque microenvironment, and provide a new framework to investigate how AD pathology might contribute to functional loss. |
format | Online Article Text |
id | pubmed-8208787 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82087872021-06-25 Rhesus monkeys as a translational model for late‐onset Alzheimer's disease Souder, Dylan C. Dreischmeier, Isabelle A. Smith, Alex B. Wright, Samantha Martin, Stephen A. Sagar, Md Abdul Kader Eliceiri, Kevin W. Salamat, Shahriar M. Bendlin, Barbara B. Colman, Ricki J. Beasley, T. Mark Anderson, Rozalyn M. Aging Cell Original Articles Age is a major risk factor for late‐onset Alzheimer's disease (AD) but seldom features in laboratory models of the disease. Furthermore, heterogeneity in size and density of AD plaques observed in individuals are not recapitulated in transgenic mouse models, presenting an incomplete picture. We show that the amyloid plaque microenvironment is not equivalent between rodent and primate species, and that differences in the impact of AD pathology on local metabolism and inflammation might explain established differences in neurodegeneration and functional decline. Using brain tissue from transgenic APP/PSEN1 mice, rhesus monkeys with age‐related amyloid plaques, and human subjects with confirmed AD, we report altered energetics in the plaque microenvironment. Metabolic features included changes in mitochondrial distribution and enzymatic activity, and changes in redox cofactors NAD(P)H that were shared among species. A greater burden of lipofuscin was detected in the brains from monkeys and humans of advanced age compared to transgenic mice. Local inflammatory signatures indexed by astrogliosis and microglial activation were detected in each species; however, the inflamed zone was considerably larger for monkeys and humans. These data demonstrate the advantage of nonhuman primates in modeling the plaque microenvironment, and provide a new framework to investigate how AD pathology might contribute to functional loss. John Wiley and Sons Inc. 2021-05-05 2021-06 /pmc/articles/PMC8208787/ /pubmed/33951283 http://dx.doi.org/10.1111/acel.13374 Text en © 2021 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Souder, Dylan C. Dreischmeier, Isabelle A. Smith, Alex B. Wright, Samantha Martin, Stephen A. Sagar, Md Abdul Kader Eliceiri, Kevin W. Salamat, Shahriar M. Bendlin, Barbara B. Colman, Ricki J. Beasley, T. Mark Anderson, Rozalyn M. Rhesus monkeys as a translational model for late‐onset Alzheimer's disease |
title | Rhesus monkeys as a translational model for late‐onset Alzheimer's disease |
title_full | Rhesus monkeys as a translational model for late‐onset Alzheimer's disease |
title_fullStr | Rhesus monkeys as a translational model for late‐onset Alzheimer's disease |
title_full_unstemmed | Rhesus monkeys as a translational model for late‐onset Alzheimer's disease |
title_short | Rhesus monkeys as a translational model for late‐onset Alzheimer's disease |
title_sort | rhesus monkeys as a translational model for late‐onset alzheimer's disease |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208787/ https://www.ncbi.nlm.nih.gov/pubmed/33951283 http://dx.doi.org/10.1111/acel.13374 |
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