ArticleActa neuropathologica2022
Dysregulated coordination of MAPT exon 2 and exon 10 splicing underlies different tau pathologies in PSP and AD.
Article in Acta neuropathologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Review
- Nitric oxide drives proteomic diversity through alternative splicing.Molecular cell · 2026Article
- SRSF1 as a promising biomarker and key player in the pathogenesis of Alzheimer's disease.Molecular medicine reports · 2026Article
- Connecting HTT intermediate alleles and microRNA dysregulation to enhanced tauopathy in late-onset Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- The splice of life: how alternative splicing shapes regulatory and phenotypic evolution.The EMBO journal · 2026Review
- Big Tau: Structure, Evolutionary Divergence, and Emerging Roles in Cytoskeletal Dynamics and Tauopathies.Cells · 2026Review
- Common and rare variant analyses implicateNPJ dementia · 2026Article
- Describing the diversity ofNPJ dementia · 2025Article
- Development of MAPT S305 mutation human iPSC lines exhibiting elevated 4R tau expression and functional alterations in neurons and astrocytes.Cell reports · 2024Article
- Article
- Understanding isoform expression by pairing long-read sequencing with single-cell and spatial transcriptomics.Genome research · 2024Review
- Lost in translation: Inconvenient truths on the utility of mouse models in Alzheimer's disease research.eLife · 2024Review
- Astrocyte tau deposition in progressive supranuclear palsy is associated with dysregulation of MAPT transcription.Acta neuropathologica communications · 2024Article
- Alterations of mRNAs and Non-coding RNAs Associated with Neuroinflammation in Alzheimer's Disease.Molecular neurobiology · 2024Review
- Pharmacotherapies for the Treatment of Progressive Supranuclear Palsy: A Narrative Review.Neurology and therapy · 2024Review
- Clinical and neuroimaging characterization of the first frontotemporal dementia family carrying the MAPT p.K298E mutation.Neurogenetics · 2024Article
- Lineage-specific splicing regulation of MAPT gene in the primate brain.Cell genomics · 2024Article
- Novel avenues of tau research.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- Unexpected gender differences in progressive supranuclear palsy reveal efficacy for davunetide in women.Translational psychiatry · 2023Article
- What's in a Gene? The Outstanding Diversity ofCells · 2022Review
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Authors and funding
12 authors at 2 institutions in 1 country.
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Abstract
Understanding regulation of MAPT splicing is important to the etiology of many nerurodegenerative diseases, including Alzheimer disease (AD) and progressive supranuclear palsy (PSP), in which different tau isoforms accumulate in pathologic inclusions. MAPT, the gene encoding the tau protein, undergoes complex alternative pre-mRNA splicing to generate six isoforms. Tauopathies can be categorized by the presence of tau aggregates containing either 3 (3R) or 4 (4R) microtubule-binding domain repeats (determined by inclusion/exclusion of exon 10), but the role of the N-terminal domain of the protein, determined by inclusion/exclusion of exons 2 and 3 has been less well studied. Using a correlational screen in human brain tissue, we observed coordination of MAPT exons 2 and 10 splicing. Expressions of exon 2 splicing regulators and subsequently exon 2 inclusion are differentially disrupted in PSP and AD brain, resulting in the accumulation of 1N4R isoforms in PSP and 0N isoforms in AD temporal cortex. Furthermore, we identified different N-terminal isoforms of tau present in neurofibrillary tangles, dystrophic neurites and tufted astrocytes, indicating a role for differential N-terminal splicing in the development of disparate tau neuropathologies. We conclude that N-terminal splicing and combinatorial regulation with exon 10 inclusion/exclusion is likely to be important to our understanding of tauopathies.
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