ArticleCellular and molecular neurobiology2024
Disease-Associated Neurotoxic Astrocyte Markers in Alzheimer Disease Based on Integrative Single-Nucleus RNA Sequencing.
Article in Cellular and molecular neurobiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 17 citations in OpenAlex.
- Neuroinflammation as molecular landscape of post-operative delirium revealed by live human brain multi-omics profiling.Molecular psychiatry · 2026Article
- Nanomedicine targeting neuroinflammatory pathways in Alzheimer's disease: a new frontier in inflammopharmacology.Inflammopharmacology · 2026Review
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- Decoding Pathogenic Mutational Landscapes in Alzheimer's Disease Through Integrated Transcriptomics.Human mutation · 2026Article
- Intracerebroventricular infusion of exercise donor plasma exosomes induces molecular changes indicating exercise-like adaptations in basal ganglia cells of older male rats.Frontiers in aging neuroscience · 2026Article
- A new role for PHYHD1 and related dioxygenases: demethylation of 2'-O-methylated nucleosides.Nucleic acids research · 2025Article
- Expression of CD44 and Its Spliced Variants: Innate and Inducible Roles in Nervous Tissue Cells and Their Environment.International journal of molecular sciences · 2025Review
- Proinflammatory transcriptomic and kinomic alterations in astrocytes derived from patients with familial Alzheimer's disease.Brain, behavior, & immunity - health · 2025Article
- Heterogeneity of Astrocyte Reactivity.Annual review of neuroscience · 2025Review
- Comparative Analysis of Human Brain RNA-seq Reveals the Combined Effects of Ferroptosis and Autophagy on Alzheimer's Disease in Multiple Brain Regions.Molecular neurobiology · 2025Article
- Glial Contribution to the Pathogenesis of Post-Operative Delirium Revealed by Multi-omic Analysis of Brain Tissue from Neurosurgery Patients.bioRxiv : the preprint server for biology · 2025Article
- Mechanisms of astrocyte aging in reactivity and disease.Molecular neurodegeneration · 2025Review
- Glioinflammation: disease-associated microglia and astrocytes in psychiatric disorders, neurodegeneration, and senescence.Frontiers in cellular neuroscience · 2025Review
- The dopamine analogue CA140 alleviates AD pathology, neuroinflammation, and rescues synaptic/cognitive functions by modulating DRD1 signaling or directly binding to Abeta.Journal of neuroinflammation · 2024Article
- Astrocytes phenomics as new druggable targets in healthy aging and Alzheimer's disease progression.Frontiers in cellular neuroscience · 2024Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Alzheimer disease (AD) is an irreversible neurodegenerative disease, and astrocytes play a key role in its onset and progression. The aim of this study is to analyze the characteristics of neurotoxic astrocytes and identify novel molecular targets for slowing down the progression of AD. Single-nucleus RNA sequencing (snRNA-seq) data were analyzed from various AD cohorts comprising about 210,654 cells from 53 brain tissue. By integrating snRNA-seq data with bulk RNA-seq data, crucial astrocyte types and genes associated with the prognosis of patients with AD were identified. The expression of neurotoxic astrocyte markers was validated using 5 × FAD and wild-type (WT) mouse models, combined with experiments such as western blot, quantitative real-time PCR (qRT-PCR), and immunofluorescence. A group of neurotoxic astrocytes closely related to AD pathology was identified, which were involved in inflammatory responses and pathways related to neuron survival. Combining snRNA and bulk tissue data, ZEP36L, AEBP1, WWTR1, PHYHD1, DST and RASL12 were identified as toxic astrocyte markers closely related to disease severity, significantly elevated in brain tissues of 5 × FAD mice and primary astrocytes treated with Aβ. Among them, WWTR1 was significantly increased in astrocytes of 5 × FAD mice, driving astrocyte inflammatory responses, and has been identified as an important marker of neurotoxic astrocytes. snRNA-seq analysis reveals the biological functions of neurotoxic astrocytes. Six genes related to AD pathology were identified and validated, among which WWTR1 may be a novel marker of neurotoxic astrocytes.
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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.