ArticleJournal of Alzheimer's disease : JAD2022
Transcriptome and Translatome Regulation of Pathogenesis in Alzheimer's Disease Model Mice.
Article in Journal of Alzheimer's disease : JAD, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 5 citations in OpenAlex.
- The use of Benzonase to produce ribosome footprints simplifies translational levels quantification by Ribo-seq.NAR genomics and bioinformatics · 2026Article
- Dysregulated mRNA Translation in Alzheimer's Disease: Mechanisms, Therapeutic Opportunities, and Challenges for Clinical Translation.Clinical interventions in aging · 2026Review
- Translational regulation and protein-coding capacity of the 5' untranslated region of human TREM2.Communications biology · 2023Article
- Advancements in Genomic and Behavioral Neuroscience Analysis for the Study of Normal and Pathological Brain Function.Frontiers in molecular neuroscience · 2022Review
- A multi-network comparative analysis of whole-transcriptome and translatome reveals the effect of high-fat diet on APP/PS1 mice and the intervention with Chinese medicine.Frontiers in nutrition · 2022Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundDefining cellular mechanisms that drive Alzheimer's disease (AD) pathogenesis and progression will be aided by studies defining how gene expression patterns change during pre-symptomatic AD and ensuing periods of declining cognition. Previous studies have emphasized changes in transcriptome, but not translatome regulation, leaving the ultimate results of gene expression alterations relatively unexplored in the context of AD.
objectiveTo identify genes whose expression might be regulated at the transcriptome and translatome levels in AD, we analyzed gene expression in cerebral cortex of two AD model mouse strains, CVN (APPSwDI;NOS2 -/- ) and Tg2576 (APPSw), and their companion wild type (WT) strains at 6 months of age by tandem RNA-Seq and Ribo-Seq (ribosome profiling).
methodsIdentical starting pools of bulk RNA were used for RNA-Seq and Ribo-Seq. Differential gene expression analysis was performed at the transcriptome, translatome, and translational efficiency levels. Regulated genes were functionally evaluated by gene ontology tools.
resultsCompared to WT mice, AD model mice had similar levels of transcriptome regulation, but differences in translatome regulation. A microglial signature associated with early stages of Aβ accumulation was upregulated at both levels in CVN mice. Although the two mice strains did not share many regulated genes, they showed common regulated pathways related to AβPP metabolism associated with neurotoxicity and neuroprotection.
conclusionThis work represents the first genome-wide study of brain translatome regulation in animal models of AD and provides evidence of a tight and early translatome regulation of gene expression controlling the balance between neuroprotective and neurodegenerative processes in brain.
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