The Bioinformatic Analysis of the Dysregulated Genes and MicroRNAs in Entorhinal Cortex, Hippocampus, and Blood for Alzheimer's Disease

Aim The incidence of Alzheimer's disease (AD) has been increasing in recent years, but there exists no cure and the pathological mechanisms are not fully understood. This study aimed to find out the pathogenesis of learning and memory impairment, new biomarkers, potential therapeutic targets, and drugs for AD. Methods We downloaded the microarray data of entorhinal cortex (EC) and hippocampus (HIP) of AD and controls from Gene Expression Omnibus (GEO) database, and then the differentially expressed genes (DEGs) in EC and HIP regions were analyzed for functional and pathway enrichment. Furthermore, we utilized the DEGs to construct coexpression networks to identify hub genes and discover the small molecules which were capable of reversing the gene expression profile of AD. Finally, we also analyzed microarray and RNA-seq dataset of blood samples to find the biomarkers related to gene expression in brain. Results We found some functional hub genes, such as ErbB2, ErbB4, OCT3, MIF, CDK13, and GPI. According to GO and KEGG pathway enrichment, several pathways were significantly dysregulated in EC and HIP. CTSD and VCAM1 were dysregulated significantly in blood, EC, and HIP, which were potential biomarkers for AD. Target genes of four microRNAs had similar GO_terms distribution with DEGs in EC and HIP. In addtion, small molecules were screened out for AD treatment. Conclusion These biological pathways and DEGs or hub genes will be useful to elucidate AD pathogenesis and identify novel biomarkers or drug targets for developing improved diagnostics and therapeutics against AD.

• Publication year

  2017

• Venue

  BioMed Research International

• Publication date

  2017-11-21

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1155/2017/9084507PMID 29359159PMCID 5735586
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• L1CAM: Cell adhesion and more.

  2016cited by this paper
• Weighted gene co-expression based biomarker discovery for psoriasis detection.

  2016cited by this paper
• Application of BACE1 immobilized enzyme reactor for the characterization of multifunctional alkaloids from Corydalis cava (Fumariaceae) as Alzheimer's disease targets.

  2016cited by this paper
• Synthesis and evaluation of multi-target-directed ligands for the treatment of Alzheimer's disease based on the fusion of donepezil and melatonin.

  2016cited by this paper
• Dysregulation of Neuregulin-1/ErbB signaling in the prefrontal cortex and hippocampus of rats exposed to chronic unpredictable mild stress.

  2016influential reference
• Exosomes in Alzheimer's disease.

  2016cited by this paper
• Plasma microRNA biomarker detection for mild cognitive impairment using differential correlation analysis

  2016influential reference
• Mitochondria as a therapeutic target in Alzheimer's disease

  2016cited by this paper
• A review on Alzheimer’s disease pathophysiology and its management: an update

  2015cited by this paper
• Alzheimer's disease risk genes and mechanisms of disease pathogenesis.

  2015cited by this paper
• Can Genetic Analysis of Putative Blood Alzheimer’s Disease Biomarkers Lead to Identification of Susceptibility Loci?

  2015cited by this paper
• Targeting Insulin Signaling for the Treatment of Alzheimer's Disease.

  2015cited by this paper
• (-)-Epigallocatechin-3-gallate attenuates cognitive deterioration in Alzheimer's disease model mice by upregulating neprilysin expression.

  2015cited by this paper
• Identification and validation of gene module associated with lung cancer through coexpression network analysis.

  2015cited by this paper
• Neuregulin-ERBB signaling in the nervous system and neuropsychiatric diseases.

  2014cited by this paper
• Cdk12 and Cdk13 regulate axonal elongation through a common signaling pathway that modulates Cdk5 expression.

  2014cited by this paper
• Neuron Review Neuregulin-ERBB Signaling in the Nervous System and Neuropsychiatric Diseases

  2014cited by this paper
• The glycolytic enzyme, GPI, is a functionally conserved modifier of dopaminergic neurodegeneration in Parkinson's models.

  2014cited by this paper
• Therapeutics of Alzheimer's disease: Past, present and future.

  2014cited by this paper
• Clustering of gene ontology terms in genomes.

  2014cited by this paper
• Synaptic genes are extensively downregulated across multiple brain regions in normal human aging and Alzheimer's disease.

  2013cited by this paper
• Genetic interactions associated with 12-month atrophy in hippocampus and entorhinal cortex in Alzheimer's Disease Neuroimaging Initiative.

  2013cited by this paper
• The Central Role of AMP-Kinase and Energy Homeostasis Impairment in Alzheimer’s Disease: A Multifactor Network Analysis

  2013cited by this paper
• A blood based 12-miRNA signature of Alzheimer disease patients

  2013influential reference
• SnapShot: genetics of Alzheimer's disease.

  2013cited by this paper
• RETRACTED: Bezafibrate improves mitochondrial function in the CNS of a mouse model of mitochondrial encephalopathy.

  2013cited by this paper
• Pathway databases: making chemical and biological sense of the genomic data flood.

  2013cited by this paper
• Classification and Natural History of the Neuronal Ceroid Lipofuscinoses

  2013cited by this paper
• Weighted Gene Coexpression Network Analysis (WGCNA) Modeling of Multiorgan Dysfunction Syndrome after Mechanical Circulatory Support Therapy

  2013cited by this paper
• Connectivity maps for biosimilar drug discovery in venoms: the case of Gila monster venom and the anti-diabetes drug Byetta®.

  2013cited by this paper
• Hippocampus neuronal metabolic gene expression outperforms whole tissue data in accurately predicting Alzheimer's disease progression.

  2012cited by this paper
• Blood-based protein biomarkers for diagnosis of Alzheimer disease.

  2012influential reference
• Bezafibrate administration improves behavioral deficits and tau pathology in P301S mice.

  2012cited by this paper
• Deficit in anterior pituitary function and variable immune deficiency (DAVID) in children presenting with adrenocorticotropin deficiency and severe infections.

  2012cited by this paper
• Strategies to explore functional genomics data sets in NCBI's GEO database.

  2012cited by this paper
• Evaluation of organic cation transporter 3 (SLC22A3) inhibition as a potential mechanism of antidepressant action.

  2012cited by this paper
• Large scale microarray profiling and coexpression network analysis of CHO cells identifies transcriptional modules associated with growth and productivity.

  2011cited by this paper
• Evaluation of the Psoriasis Transcriptome across Different Studies by Gene Set Enrichment Analysis (GSEA)

  2010cited by this paper
• Neuronal gene expression in non-demented individuals with intermediate Alzheimer's Disease neuropathology.

  2010cited by this paper
• Soluble cell adhesion molecules in monocytes of Alzheimer's disease and mild cognitive impairment.

  2010cited by this paper
• Drosophila notal bristle as a novel assessment tool for pathogenic study of Tau toxicity and screening of therapeutic compounds.

  2010cited by this paper
• ErbB receptors and the development of the nervous system.

  2009influential reference
• Suppressive effects of flavonoid fisetin on lipopolysaccharide-induced microglial activation and neurotoxicity.

  2008cited by this paper
• Muscarinic acetylcholine receptor-dependent induction of persistent synaptic enhancement in rat hippocampus in vivo.

  2007cited by this paper
• The Connectivity Map: a new tool for biomedical research

  2007cited by this paper
• Transcriptional profiling of Alzheimer blood mononuclear cells by microarray.

  2007influential reference
• Gene expression profiles in anatomically and functionally distinct regions of the normal aged human brain.

  2007cited by this paper
• Cooperation between the hippocampus and the entorhinal cortex in spatial memory: a disconnection study.

  2006cited by this paper
• Age effects on atrophy rates of entorhinal cortex and hippocampus.

  2006cited by this paper
• Cathepsin D deficiency underlies congenital human neuronal ceroid-lipofuscinosis.

  2006cited by this paper
• Interaction of CTSD and A2M polymorphisms in the risk for Alzheimer's disease.

  2006cited by this paper
• Akt activity in Alzheimer's disease and other neurodegenerative disorders

  2004cited by this paper
• The synaptic vesicle cycle.

  2004cited by this paper
• Gene Expression Omnibus: NCBI gene expression and hybridization array data repository

  2002cited by this paper

• Exploring the Role of microRNAs as Blood Biomarkers in Alzheimer’s Disease and Frontotemporal Dementia

  2025cites this paper
• 3DSTarPred: A Web Server for Target Prediction of Bioactive Small Molecules Based on 3D Shape Similarity

  2024cites this paper
• O-demethyl galantamine alters protein expression in cerebellum of 5xFAD mice

  2024cites this paper
• Identification of Alzheimer’s Disease Hub Genes Based on Improved HITS Algorithm

  2024cites this paper
• Translational bioinformatics and data science for biomarker discovery in mental health: an analytical review

  2024cites this paper
• A review and analysis of key biomarkers in Alzheimer’s disease

  2024cites this paper
• Sex-associated microRNAs potentially implicated in sporadic Alzheimer's disease (sAD).

  2024cites this paper
• Unraveling the role of miRNAs in the diagnosis, progression, and therapeutic intervention of Alzheimer's disease.

  2023cites this paper
• Data Mining of Microarray Datasets in Translational Neuroscience

  2023cites this paper
• AR12 increases BAG3 expression which is essential for Tau and APP degradation via LC3-associated phagocytosis and macroautophagy

  2022cites this paper
• Bioinformatics-based study reveals that AP2M1 is regulated by the circRNA-miRNA-mRNA interaction network and affects Alzheimer’s disease

  2022cites this paper
• AR12 increases BAG3 expression via ER stress signaling which is essential for Tau and APP degradation via LC3-associated phagocytosis and macroautophagy

  2022cites this paper
• Identification of blood-based transcriptomics biomarkers for Alzheimer's disease using statistical and machine learning classifier

  2022cites this paper
• Bioinformatics analysis of differentially expressed genes and identification of an miRNA–mRNA network associated with entorhinal cortex and hippocampus in Alzheimer’s disease

  2021cites this paper
• Machine learning compensates fold-change method and highlights oxidative phosphorylation in the brain transcriptome of Alzheimer’s disease

  2021cites this paper
• Admixture mapping reveals the association between Native American ancestry at 3q13.11 and reduced risk of Alzheimer’s disease in Caribbean Hispanics

  2021cites this paper
• Inhibition of heat shock proteins increases autophagosome formation, and reduces the expression of APP, Tau, SOD1 G93A and TDP-43

  2021cites this paper
• Defining the Dynamic Regulation of O-GlcNAc Proteome in the Mouse Cortex---the O-GlcNAcylation of Synaptic and Trafficking Proteins Related to Neurodegenerative Diseases

  2021cites this paper
• Molecular Pathogenesis and Interventional Strategies for Alzheimer's Disease: Promises and Pitfalls.

  2020cites this paper
• A Systematic Bioinformatics Workflow With Meta-Analytics Identified Potential Pathogenic Factors of Alzheimer’s Disease

  2020cites this paper
• Prediction of hub genes of Alzheimer’s disease using a protein interaction network and functional enrichment analysis

  2020cites this paper
• Identification of Key Regulatory Genes and Pathways in Prefrontal Cortex of Alzheimer’s Disease

  2020cites this paper
• Corticohippocampal Neuroenergetics and histomorphology in aluminium-induced neurotoxicity: Putative therapeutic roles of ascorbic acid and nicotine

  2020cites this paper
• Integrated identification of key genes and pathways in Alzheimer’s disease via comprehensive bioinformatical analyses

  2019cites this paper
• MicroRNAs in Alzheimer’s Disease: Diagnostic Markers or Therapeutic Agents?

  2019cites this paper
• Blood‐based redox‐signature and their association to the cognitive scores in MCI and Alzheimer’s disease patients

  2019cites this paper
• Identification of key genes and pathways contributing to artery tertiary lymphoid organ development in advanced mouse atherosclerosis

  2019cites this paper
• Identification of Potential Biomarker Using Combined Analysis of Differentially Expressed Genes and miRNAs for Alzheimer’s Disease

  2019cites this paper
• Apigenin-rivastigmine hybrids as multi-target-directed liagnds for the treatment of Alzheimer's disease.

  2019cites this paper
• Mouse Model of Congenital Heart Defects, Dysmorphic Facial Features and Intellectual Developmental Disorders as a Result of Non-functional CDK13

  2019cites this paper
• The current status of blood epigenetic biomarkers for dementia

  2019influential citation