Mega-Analysis of Gene Expression in Mouse Models of Alzheimer’s Disease

Zhuang, Beryl; Mancarci, B. Ogan; Toker, Lilah; Pavlidis, Paul

doi:10.1523/eneuro.0226-19.2019

Cited by 8 publications

(2 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cholesterol biosynthesis and SREBF1 were strongly enriched in the AD‐metabolic transcriptome, which was predominantly derived from AD mice modeling amyloid deposition. In agreement with our findings, abnormal levels of cholesterol and its sterol intermediates have been reported in the brain metabolome (Chan et al, 2012) and transcriptome (Zhuang et al, 2019) of AD mice harboring pathogenic mutations in their APP and PS1 loci. The AD‐metabolic transcriptome also exhibited a significant microglia enrichment, thus suggesting microglial cholesterol metabolism might play an important role in AD pathogenesis.…”

Section: Discussionsupporting

confidence: 93%

Pathway‐based integration of multi‐omics data reveals lipidomics alterations validated in an Alzheimer's disease mouse model and risk loci carriers

Garcia‐Segura

Durainayagam

Liggi

et al. 2022

Journal of Neurochemistry

View full text Add to dashboard Cite

Alzheimer´s Disease (AD) is a highly prevalent neurodegenerative disorder. Despite increasing evidence of the importance of metabolic dysregulation in AD, the underlying metabolic changes that may impact amyloid plaque formation are not understood, particularly for late onset AD. This study analyzed genome-wide association studies (GWAS), transcriptomics and proteomics data obtained from several data repositories to obtain differentially expressed (DE) multi-omics elements in mouse models of AD. We characterized the metabolic modulation in these datasets using gene ontology, transcription factor, pathway, and cell-type enrichment analyses. A predicted lipid signature was extracted from genome-scale metabolic networks (GSMN) and subsequently validated in a lipidomic dataset derived from cortical tissue of ABCA-7 null mice, a mouse model of one of the genes associated with late onset AD. Moreover, a metabolome-wide association study (MWAS) was performed to further characterize the association between dysregulated lipid metabolism in human blood serum and genes associated with AD risk. We found 203 DE transcripts, 164 DE proteins and 58 DE GWAS-derived mouse orthologs associated with significantly enriched metabolic biological processes. Lipid and bioenergetics metabolic pathways were significantly over-represented across the AD multi-omics datasets. Microglia and astrocytes were significantly enriched in the lipid-predominant AD-metabolic This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as

show abstract

Section: Discussionsupporting

confidence: 93%

Pathway‐based integration of multi‐omics data reveals lipidomics alterations validated in an Alzheimer's disease mouse model and risk loci carriers

Garcia‐Segura

Durainayagam

Liggi

et al. 2022

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…Genetic predisposition and epigenetic mechanisms have been consistently reported to play critical roles in AD pathogenesis. [68][69][70] These observations were further substantiated in the study by Mastroeni et al, 15 which found reduced 5mC staining and decreased expression of several DNA methylation factors, such as DNMT1 and the MeCP1/MBD2 complex, in the EC of postmortem AD brains. Given the role of epigenetics in global genomic regulation, the consequences of these epigenetic alterations in AD will be rather diverse.…”

Section: Neurochemical Processesmentioning

confidence: 61%

DNA methylation in the pathology of Alzheimer's disease: from gene to cognition

Poon

Tse

Lim

2020

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

Alzheimer's disease (AD) is a debilitating disorder that manifests with amyloid beta plaque deposition, neurofibrillary tangles, neuronal loss, and severe cognitive impairment. Although much effort has been made to decipher the pathogenesis of this disease, the mechanisms causing these detrimental outcomes remain obscure. Over the past few decades, neuroepigenetics has emerged as an important field that, among other things, explores how reversible modifications can change gene expression to control behavior and cognitive abilities. Among epigenetic modifications, DNA methylation requires further elucidation for the conflicting observations from AD research and its pivotal role in learning and memory. In this review, we focus on the essential components of DNA methylation, the effects of aberrant methylation on gene expressions in the amyloidogenic pathway and neurochemical processes, as well as memory epigenetics in Alzheimer's disease.

show abstract