Transcriptomic Changes Highly Similar to Alzheimer’s Disease Are Observed in a Subpopulation of Individuals During Normal Brain Aging

Aging is a major risk factor for late-onset Alzheimer’s disease (LOAD). How aging contributes to the development of LOAD remains elusive. In this study, we examined multiple large-scale transcriptomic datasets from both normal aging and LOAD brains to understand the molecular interconnection between...

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Auteurs principaux:	Shouneng Peng, Lu Zeng, Jean-Vianney Haure-Mirande, Minghui Wang, Derek M. Huffman, Vahram Haroutunian, Michelle E. Ehrlich, Bin Zhang, Zhidong Tu
Format:	article
Langue:	EN
Publié:	Frontiers Media S.A. 2021
Sujets:	aging brain late-onset Alzheimer’s disease human brain transcriptome RNAseq brain aging subgroups hippocampus Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Accès en ligne:	https://doaj.org/article/edd42ca4f7c84ac29d263d4073145dca
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spelling	oai:doaj.org-article:edd42ca4f7c84ac29d263d4073145dca2021-12-02T11:54:33ZTranscriptomic Changes Highly Similar to Alzheimer’s Disease Are Observed in a Subpopulation of Individuals During Normal Brain Aging1663-436510.3389/fnagi.2021.711524https://doaj.org/article/edd42ca4f7c84ac29d263d4073145dca2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnagi.2021.711524/fullhttps://doaj.org/toc/1663-4365Aging is a major risk factor for late-onset Alzheimer’s disease (LOAD). How aging contributes to the development of LOAD remains elusive. In this study, we examined multiple large-scale transcriptomic datasets from both normal aging and LOAD brains to understand the molecular interconnection between aging and LOAD. We found that shared gene expression changes between aging and LOAD are mostly seen in the hippocampal and several cortical regions. In the hippocampus, the expression of phosphoprotein, alternative splicing and cytoskeleton genes are commonly changed in both aging and AD, while synapse, ion transport, and synaptic vesicle genes are commonly down-regulated. Aging-specific changes are associated with acetylation and methylation, while LOAD-specific changes are more related to glycoprotein (both up- and down-regulations), inflammatory response (up-regulation), myelin sheath and lipoprotein (down-regulation). We also found that normal aging brain transcriptomes from relatively young donors (45–70 years old) clustered into several subgroups and some subgroups showed gene expression changes highly similar to those seen in LOAD brains. Using brain transcriptomic datasets from another cohort of older individuals (>70 years), we found that samples from cognitively normal older individuals clustered with the “healthy aging” subgroup while AD samples mainly clustered with the “AD similar” subgroups. This may imply that individuals in the healthy aging subgroup will likely remain cognitively normal when they become older and vice versa. In summary, our results suggest that on the transcriptome level, aging and LOAD have strong interconnections in some brain regions in a subpopulation of cognitively normal aging individuals. This supports the theory that the initiation of LOAD occurs decades earlier than the manifestation of clinical phenotype and it may be essential to closely study the “normal brain aging” to identify the very early molecular events that may lead to LOAD development.Shouneng PengShouneng PengShouneng PengLu ZengLu ZengLu ZengJean-Vianney Haure-MirandeMinghui WangMinghui WangMinghui WangDerek M. HuffmanDerek M. HuffmanDerek M. HuffmanVahram HaroutunianVahram HaroutunianVahram HaroutunianMichelle E. EhrlichMichelle E. EhrlichMichelle E. EhrlichBin ZhangBin ZhangBin ZhangZhidong TuZhidong TuZhidong TuFrontiers Media S.A.articleaging brainlate-onset Alzheimer’s diseasehuman brain transcriptomeRNAseqbrain aging subgroupshippocampusNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Aging Neuroscience, Vol 13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	aging brain late-onset Alzheimer’s disease human brain transcriptome RNAseq brain aging subgroups hippocampus Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	aging brain late-onset Alzheimer’s disease human brain transcriptome RNAseq brain aging subgroups hippocampus Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Shouneng Peng Shouneng Peng Shouneng Peng Lu Zeng Lu Zeng Lu Zeng Jean-Vianney Haure-Mirande Minghui Wang Minghui Wang Minghui Wang Derek M. Huffman Derek M. Huffman Derek M. Huffman Vahram Haroutunian Vahram Haroutunian Vahram Haroutunian Michelle E. Ehrlich Michelle E. Ehrlich Michelle E. Ehrlich Bin Zhang Bin Zhang Bin Zhang Zhidong Tu Zhidong Tu Zhidong Tu Transcriptomic Changes Highly Similar to Alzheimer’s Disease Are Observed in a Subpopulation of Individuals During Normal Brain Aging
description	Aging is a major risk factor for late-onset Alzheimer’s disease (LOAD). How aging contributes to the development of LOAD remains elusive. In this study, we examined multiple large-scale transcriptomic datasets from both normal aging and LOAD brains to understand the molecular interconnection between aging and LOAD. We found that shared gene expression changes between aging and LOAD are mostly seen in the hippocampal and several cortical regions. In the hippocampus, the expression of phosphoprotein, alternative splicing and cytoskeleton genes are commonly changed in both aging and AD, while synapse, ion transport, and synaptic vesicle genes are commonly down-regulated. Aging-specific changes are associated with acetylation and methylation, while LOAD-specific changes are more related to glycoprotein (both up- and down-regulations), inflammatory response (up-regulation), myelin sheath and lipoprotein (down-regulation). We also found that normal aging brain transcriptomes from relatively young donors (45–70 years old) clustered into several subgroups and some subgroups showed gene expression changes highly similar to those seen in LOAD brains. Using brain transcriptomic datasets from another cohort of older individuals (>70 years), we found that samples from cognitively normal older individuals clustered with the “healthy aging” subgroup while AD samples mainly clustered with the “AD similar” subgroups. This may imply that individuals in the healthy aging subgroup will likely remain cognitively normal when they become older and vice versa. In summary, our results suggest that on the transcriptome level, aging and LOAD have strong interconnections in some brain regions in a subpopulation of cognitively normal aging individuals. This supports the theory that the initiation of LOAD occurs decades earlier than the manifestation of clinical phenotype and it may be essential to closely study the “normal brain aging” to identify the very early molecular events that may lead to LOAD development.
format	article
author	Shouneng Peng Shouneng Peng Shouneng Peng Lu Zeng Lu Zeng Lu Zeng Jean-Vianney Haure-Mirande Minghui Wang Minghui Wang Minghui Wang Derek M. Huffman Derek M. Huffman Derek M. Huffman Vahram Haroutunian Vahram Haroutunian Vahram Haroutunian Michelle E. Ehrlich Michelle E. Ehrlich Michelle E. Ehrlich Bin Zhang Bin Zhang Bin Zhang Zhidong Tu Zhidong Tu Zhidong Tu
author_facet	Shouneng Peng Shouneng Peng Shouneng Peng Lu Zeng Lu Zeng Lu Zeng Jean-Vianney Haure-Mirande Minghui Wang Minghui Wang Minghui Wang Derek M. Huffman Derek M. Huffman Derek M. Huffman Vahram Haroutunian Vahram Haroutunian Vahram Haroutunian Michelle E. Ehrlich Michelle E. Ehrlich Michelle E. Ehrlich Bin Zhang Bin Zhang Bin Zhang Zhidong Tu Zhidong Tu Zhidong Tu
author_sort	Shouneng Peng
title	Transcriptomic Changes Highly Similar to Alzheimer’s Disease Are Observed in a Subpopulation of Individuals During Normal Brain Aging
title_short	Transcriptomic Changes Highly Similar to Alzheimer’s Disease Are Observed in a Subpopulation of Individuals During Normal Brain Aging
title_full	Transcriptomic Changes Highly Similar to Alzheimer’s Disease Are Observed in a Subpopulation of Individuals During Normal Brain Aging
title_fullStr	Transcriptomic Changes Highly Similar to Alzheimer’s Disease Are Observed in a Subpopulation of Individuals During Normal Brain Aging
title_full_unstemmed	Transcriptomic Changes Highly Similar to Alzheimer’s Disease Are Observed in a Subpopulation of Individuals During Normal Brain Aging
title_sort	transcriptomic changes highly similar to alzheimer’s disease are observed in a subpopulation of individuals during normal brain aging
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/edd42ca4f7c84ac29d263d4073145dca
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Transcriptomic Changes Highly Similar to Alzheimer’s Disease Are Observed in a Subpopulation of Individuals During Normal Brain Aging

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