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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
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.
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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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