Comprehensive transcript-level analysis reveals transcriptional reprogramming during the progression of Alzheimer's disease.

Background: Alzheimer's disease (AD) is a common neurodegenerative disorder that has a multi-step disease progression. Differences between moderate and advanced stages of AD have not yet been fully characterized. Materials and methods: Herein, we performed a transcript-resolution analysis in 454 AD-...

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Publicado en:Frontiers in Aging Neuroscience pp. 1 - 12
Autores principales: Hao Wu, Jiao Wang, Xiaoyuan Hu, Cheng Zhuang, Jianxin Zhou, Peiru Wu, Shengli Li, Chunhua Zhao, Robert
Formato: equations & formulas research tables/charts Journal Article
Publicado: Frontiers Media S.A. 2023
Acceso en línea:Ver este registro en EBSCOhost
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      jtl: Frontiers in Aging Neuroscience
      issn: 16634365
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      dt: 2023
      pid: 40038
      pub: Frontiers Media S.A.
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        164605173
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        10.3389/fnagi.2023.1191680
        164605173
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        atl: Comprehensive transcript-level analysis reveals transcriptional reprogramming during the progression of Alzheimer's disease.
      aug:
        au:
          Hao Wu
          Jiao Wang
          Xiaoyuan Hu
          Cheng Zhuang
          Jianxin Zhou
          Peiru Wu
          Shengli Li
          Chunhua Zhao, Robert
        affil: Laboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai, China
      sug:
        subj:
          Alzheimer's Disease
          Disease Progression
          Gene Expression Profiling
          Human
          Descriptive Statistics
          Data Analysis Software
          Spearman's Rank Correlation Coefficient
          Funding Source
          Comparative Studies
          RNA-Binding Proteins Metabolism
          Biological Markers
          Pearson's Correlation Coefficient
          Early Diagnosis
      ab: Background: Alzheimer's disease (AD) is a common neurodegenerative disorder that has a multi-step disease progression. Differences between moderate and advanced stages of AD have not yet been fully characterized. Materials and methods: Herein, we performed a transcript-resolution analysis in 454 AD-related samples, including 145 non-demented control, 140 asymptomatic AD (AsymAD), and 169 AD samples. We comparatively characterized the transcriptome dysregulation in AsymAD and AD samples at transcript level. Results: We identified 4,056 and 1,200 differentially spliced alternative splicing events (ASEs) that might play roles in the disease progression of AsymAD and AD, respectively. Our further analysis revealed 287 and 222 isoform switching events in AsymAD and AD, respectively. In particular, a total of 163 and 119 transcripts showed increased usage, while 124 and 103 transcripts exhibited decreased usage in AsymAD and AD, respectively. For example, gene APOA2 showed no expression changes between AD and non-demented control samples, but expressed higher proportion of transcript ENST00000367990.3 and lower proportion of transcript ENST00000463812.1 in AD compared to non-demented control samples. Furthermore, we constructed RNA binding protein (RBP)-ASE regulatory networks to reveal potential RBP-mediated isoform switch in AsymAD and AD. Conclusion: In summary, our study provided transcript-resolution insights into the transcriptome disturbance of AsymAD and AD, which will promote the discovery of early diagnosis biomarkers and the development of new therapeutic strategies for patients with AD.
      pubtype: Academic Journal
      doctype:
        equations & formulas
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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