ArticleGenome research2011
Analysis of alternative splicing associated with aging and neurodegeneration in the human brain.
Article in Genome research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers.
What it found
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Who cites it
151 citing papers in PubMed, 253 citations in OpenAlex.
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- Identification of small ubiquitin-related modifier (SUMO)-related genes-based biomarkers in Alzheimer's disease based on bioinformatics analysis.Scientific reports · 2026Article
- Inhibiting Glycogen Synthase Kinase 3 Suppresses TDP-43-Mediated Neurotoxicity in a Caspase-Dependent Manner.Molecular neurobiology · 2026Article
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- Alternative splicing and the aging brain in AfrAbia: New frontiers in dementia research.IBRO neuroscience reports · 2025Article
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- Age-related microbiome metabolites alter RNA splicing and chromatin accessibility in the brain.bioRxiv : the preprint server for biology · 2025Article
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- Dominant-negative isoform of TDP-43 is regulated by ALS-linked RNA-binding proteins.The Journal of cell biology · 2025Article
- Differential effects of age and sex on tau pathology propagation in the htau mouse model: A neuropathological and proteomic study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- SFRS8 Regulates Memory by Modulating RNA Splicing of Synaptic Genes.Molecular neurobiology · 2025Article
- Transcript diversity in aging: cryptic transcription and splicing.Medical review (2021) · 2025Review
- A spatial long-read approach at near-single-cell resolution reveals developmental regulation of splicing and polyadenylation sites in distinct cortical layers and cell types.Nature communications · 2025Article
- Methylome analysis of FTLD patients with TDP-43 pathology identifies epigenetic signatures specific to pathological subtypes.Molecular neurodegeneration · 2025Article
- Analysis of the splicing landscape of the frontal cortex in FTLD-TDP reveals subtype specific patterns and cryptic splicing.Acta neuropathologica · 2025Article
- Structural and functional insights into the nuclear role of Parkinson's disease-associated α-synuclein as a histone chaperone.Communications biology · 2025Article
- A computational framework for detecting inter-tissue gene-expression coordination changes with aging.Scientific reports · 2025Article
91 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
Age is the most important risk factor for neurodegeneration; however, the effects of aging and neurodegeneration on gene expression in the human brain have most often been studied separately. Here, we analyzed changes in transcript levels and alternative splicing in the temporal cortex of individuals of different ages who were cognitively normal, affected by frontotemporal lobar degeneration (FTLD), or affected by Alzheimer's disease (AD). We identified age-related splicing changes in cognitively normal individuals and found that these were present also in 95% of individuals with FTLD or AD, independent of their age. These changes were consistent with increased polypyrimidine tract binding protein (PTB)-dependent splicing activity. We also identified disease-specific splicing changes that were present in individuals with FTLD or AD, but not in cognitively normal individuals. These changes were consistent with the decreased neuro-oncological ventral antigen (NOVA)-dependent splicing regulation, and the decreased nuclear abundance of NOVA proteins. As expected, a dramatic down-regulation of neuronal genes was associated with disease, whereas a modest down-regulation of glial and neuronal genes was associated with aging. Whereas our data indicated that the age-related splicing changes are regulated independently of transcript-level changes, these two regulatory mechanisms affected expression of genes with similar functions, including metabolism and DNA repair. In conclusion, the alternative splicing changes identified in this study provide a new link between aging and neurodegeneration.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.