ArticleScience advances2020
Dedifferentiation and neuronal repression define familial Alzheimer's disease.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 6 citations in OpenAlex.
- MECP2Science China. Life sciences · 2026Article
- Resistance of E2F4DN to p38Scientific reports · 2026Article
- Phosphorylated ubiquitin is a secondary messenger and an epigenetic mark mediating mitochondria to nucleus signaling.bioRxiv : the preprint server for biology · 2026Article
- Epigenomic aberrations of histone methylation in prefrontal cortex of humans with mild cognitive impairment and Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2026Article
- Modeling Late-Onset Sporadic Alzheimer's Disease Using Patient-Derived Cells: A Review.Neurology international · 2026Review
- Pyruvate kinase M2 in Alzheimer's disease: from dysregulation to therapeutic inhibition.Brain communications · 2026Review
- Ovarian germline stem cell dedifferentiation is cytoneme dependent.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Chromatin accessibility provides a window into the genetic etiology of human brain disease.Trends in genetics : TIG · 2025Review
- Integrative multiomics reveals common endotypes across PSEN1, PSEN2, and APP mutations in familial Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- Macroscale connectome topographical structure reveals the biomechanisms of brain dysfunction in Alzheimer's disease.Science advances · 2024Article
- pyPAGE: A framework for Addressing biases in gene-set enrichment analysis-A case study on Alzheimer's disease.PLoS computational biology · 2024Article
- Xenografted human iPSC-derived neurons with the familial Alzheimer's disease APPActa neuropathologica · 2024Article
- A novel APP splice variant-dependent marker system to precisely demarcate maturity in SH-SY5Y cell-derived neurons.Scientific reports · 2024Article
- A multi-looping chromatin signature predicts dysregulated gene expression in neurons with familial Alzheimer's disease mutations.bioRxiv : the preprint server for biology · 2024Article
- Cerebrospinal fluid proteomics in patients with Alzheimer's disease reveals five molecular subtypes with distinct genetic risk profiles.Nature aging · 2024Article
- Limitations of the human iPSC-derived neuron model for early-onset Alzheimer's disease.Molecular brain · 2023Article
- Alzheimer's disease and related tauopathies: disorders of disrupted neuronal identity.Trends in neurosciences · 2023Review
- Article
- Neural cell state shifts and fate loss in ageing and age-related diseases.Nature reviews. Neurology · 2023Review
- Integrated multimodal cell atlas of Alzheimer's disease.Research square · 2023Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Identifying the systems-level mechanisms that lead to Alzheimer's disease, an unmet need, is an essential step toward the development of therapeutics. In this work, we report that the key disease-causative mechanisms, including dedifferentiation and repression of neuronal identity, are triggered by changes in chromatin topology. Here, we generated human induced pluripotent stem cell (hiPSC)-derived neurons from donor patients with early-onset familial Alzheimer's disease (EOFAD) and used a multiomics approach to mechanistically characterize the modulation of disease-associated gene regulatory programs. We demonstrate that EOFAD neurons dedifferentiate to a precursor-like state with signatures of ectoderm and nonectoderm lineages. RNA-seq, ATAC-seq, and ChIP-seq analysis reveals that transcriptional alterations in the cellular state are orchestrated by changes in histone methylation and chromatin topology. Furthermore, we demonstrate that these mechanisms are observed in EOFAD-patient brains, validating our hiPSC-derived neuron models. The mechanistic endotypes of Alzheimer's disease uncovered here offer key insights for therapeutic interventions.
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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.