Revealing the Molecular Mechanisms of Alzheimer’s Disease Based on Network Analysis

Revealing the Molecular Mechanisms of Alzheimer’s Disease Based on Network Analysis

The complex pathology of Alzheimer’s disease (AD) emphasises the need for comprehensive modelling of the disease, which may lead to the development of efficient treatment strategies. To address this challenge, we analysed transcriptome data of post-mortem human brain samples of healthy elders and in...

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Autores principales: Abdulahad Bayraktar, Simon Lam, Ozlem Altay, Xiangyu Li, Meng Yuan, Cheng Zhang, Muhammad Arif, Hasan Turkez, Mathias Uhlén, Saeed Shoaie, Adil Mardinoglu
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
Materias:
Alzheimer’s disease
gene co-expression network
genome-scale metabolic model
reporter metabolite analysis
energy metabolism
Biology (General)
QH301-705.5
Chemistry
QD1-999
Acceso en línea:https://doaj.org/article/9d63a20cc32b49bab93cf1a8655cf91a
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spelling oai:doaj.org-article:9d63a20cc32b49bab93cf1a8655cf91a2021-11-11T17:02:26ZRevealing the Molecular Mechanisms of Alzheimer’s Disease Based on Network Analysis10.3390/ijms2221115561422-00671661-6596https://doaj.org/article/9d63a20cc32b49bab93cf1a8655cf91a2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11556https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The complex pathology of Alzheimer’s disease (AD) emphasises the need for comprehensive modelling of the disease, which may lead to the development of efficient treatment strategies. To address this challenge, we analysed transcriptome data of post-mortem human brain samples of healthy elders and individuals with late-onset AD from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP) and Mayo Clinic (MayoRNAseq) studies in the AMP-AD consortium. In this context, we conducted several bioinformatics and systems medicine analyses including the construction of AD-specific co-expression networks and genome-scale metabolic modelling of the brain in AD patients to identify key genes, metabolites and pathways involved in the progression of AD. We identified <i>AMIGO1</i> and <i>GRPRASP2</i> as examples of commonly altered marker genes in AD patients. Moreover, we found alterations in energy metabolism, represented by reduced oxidative phosphorylation and ATPase activity, as well as the depletion of hexanoyl-CoA, pentanoyl-CoA, (2E)-hexenoyl-CoA and numerous other unsaturated fatty acids in the brain. We also observed that neuroprotective metabolites (e.g., vitamins, retinoids and unsaturated fatty acids) tend to be depleted in the AD brain, while neurotoxic metabolites (e.g., β-alanine, bilirubin) were more abundant. In summary, we systematically revealed the key genes and pathways related to the progression of AD, gained insight into the crucial mechanisms of AD and identified some possible targets that could be used in the treatment of AD.Abdulahad BayraktarSimon LamOzlem AltayXiangyu LiMeng YuanCheng ZhangMuhammad ArifHasan TurkezMathias UhlénSaeed ShoaieAdil MardinogluMDPI AGarticleAlzheimer’s diseasegene co-expression networkgenome-scale metabolic modelreporter metabolite analysisenergy metabolismBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11556, p 11556 (2021)
institution DOAJ
collection DOAJ
language EN
topic Alzheimer’s disease
gene co-expression network
genome-scale metabolic model
reporter metabolite analysis
energy metabolism
Biology (General)
QH301-705.5
Chemistry
QD1-999
spellingShingle Alzheimer’s disease
gene co-expression network
genome-scale metabolic model
reporter metabolite analysis
energy metabolism
Biology (General)
QH301-705.5
Chemistry
QD1-999
Abdulahad Bayraktar
Simon Lam
Ozlem Altay
Xiangyu Li
Meng Yuan
Cheng Zhang
Muhammad Arif
Hasan Turkez
Mathias Uhlén
Saeed Shoaie
Adil Mardinoglu
Revealing the Molecular Mechanisms of Alzheimer’s Disease Based on Network Analysis
description The complex pathology of Alzheimer’s disease (AD) emphasises the need for comprehensive modelling of the disease, which may lead to the development of efficient treatment strategies. To address this challenge, we analysed transcriptome data of post-mortem human brain samples of healthy elders and individuals with late-onset AD from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP) and Mayo Clinic (MayoRNAseq) studies in the AMP-AD consortium. In this context, we conducted several bioinformatics and systems medicine analyses including the construction of AD-specific co-expression networks and genome-scale metabolic modelling of the brain in AD patients to identify key genes, metabolites and pathways involved in the progression of AD. We identified <i>AMIGO1</i> and <i>GRPRASP2</i> as examples of commonly altered marker genes in AD patients. Moreover, we found alterations in energy metabolism, represented by reduced oxidative phosphorylation and ATPase activity, as well as the depletion of hexanoyl-CoA, pentanoyl-CoA, (2E)-hexenoyl-CoA and numerous other unsaturated fatty acids in the brain. We also observed that neuroprotective metabolites (e.g., vitamins, retinoids and unsaturated fatty acids) tend to be depleted in the AD brain, while neurotoxic metabolites (e.g., β-alanine, bilirubin) were more abundant. In summary, we systematically revealed the key genes and pathways related to the progression of AD, gained insight into the crucial mechanisms of AD and identified some possible targets that could be used in the treatment of AD.
format article
author Abdulahad Bayraktar
Simon Lam
Ozlem Altay
Xiangyu Li
Meng Yuan
Cheng Zhang
Muhammad Arif
Hasan Turkez
Mathias Uhlén
Saeed Shoaie
Adil Mardinoglu
author_facet Abdulahad Bayraktar
Simon Lam
Ozlem Altay
Xiangyu Li
Meng Yuan
Cheng Zhang
Muhammad Arif
Hasan Turkez
Mathias Uhlén
Saeed Shoaie
Adil Mardinoglu
author_sort Abdulahad Bayraktar
title Revealing the Molecular Mechanisms of Alzheimer’s Disease Based on Network Analysis
title_short Revealing the Molecular Mechanisms of Alzheimer’s Disease Based on Network Analysis
title_full Revealing the Molecular Mechanisms of Alzheimer’s Disease Based on Network Analysis
title_fullStr Revealing the Molecular Mechanisms of Alzheimer’s Disease Based on Network Analysis
title_full_unstemmed Revealing the Molecular Mechanisms of Alzheimer’s Disease Based on Network Analysis
title_sort revealing the molecular mechanisms of alzheimer’s disease based on network analysis
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/9d63a20cc32b49bab93cf1a8655cf91a
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