ArticleExperimental & molecular medicine2023
Spatiotemporal characterization of glial cell activation in an Alzheimer's disease model by spatially resolved transcriptomics.
Article in Experimental & molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Regional astrocyte dysregulation and altered glymphatic-related markers in Alzheimer's disease frontal cortex.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Targeting the astrocyte-microglia EFEMP1-GALNT10 axis: a spatially programmable therapeutic strategy for hippocampal vulnerability in Alzheimer's disease.Journal of translational medicine · 2026Article
- Spatial transcriptomics in Alzheimer's disease: technologies, challenges and discoveries.Molecular neurodegeneration advances · 2026Review
- Glial-Dopamine crosstalk: Astrocytic and microglial gatekeepers of neuroinflammation, plasticity, and motivation.AIMS neuroscience · 2026Review
- sc4D: spatio-temporal single-cell transcriptomics analysis through embedded optimal transport identifies joint glial response to Alzheimer's disease pathology.bioRxiv : the preprint server for biology · 2025Article
- Deciphering context-specific gene programs from single-cell and spatial transcriptomics data with DeCEP.Genome research · 2025Article
- Super-Resolved Spatial Transcriptomics Reveals Early Changes in RNA Localization in the 5xFAD Hippocampus.bioRxiv : the preprint server for biology · 2025Article
- Isotope-encoded spatial biology identifies plaque-age-dependent maturation and synaptic loss in an Alzheimer's disease mouse model.Nature communications · 2025Article
- Alzheimer's disease brain-derived tau extracts show differential processing and transcriptional effects in human astrocytes.iScience · 2025Article
- Biomarkers and therapeutic strategies targeting microglia in neurodegenerative diseases: current status and future directions.Molecular neurodegeneration · 2025Review
- Review
- Spatial transcriptomics reveals an unexpected impact of tau and tau pathology on the expression of transthyretin.Frontiers in aging neuroscience · 2025Article
- Spatial Transcriptomic Analysis Identifies abioRxiv : the preprint server for biology · 2024Article
- Isotope Encoded chemical Imaging Identifies Amyloid Plaque Age Dependent Structural Maturation, Synaptic Loss, and Increased Toxicity.bioRxiv : the preprint server for biology · 2024Article
- Orchestration of antiviral responses within the infected central nervous system.Cellular & molecular immunology · 2024Review
- Spatiotemporal Dysregulation of Neuron-Glia Related Genes and Pro-/Anti-Inflammatory miRNAs in theInternational journal of molecular sciences · 2024Article
- SpatialSPM: statistical parametric mapping for the comparison of gene expression pattern images in multiple spatial transcriptomic datasets.Nucleic acids research · 2024Article
- Advances in Single-Cell Transcriptome Sequencing and Spatial Transcriptome Sequencing in Plants.Plants (Basel, Switzerland) · 2024Review
- Spatial transcriptomic brain imaging reveals the effects of immunomodulation therapy on specific regional brain cells in a mouse dementia model.BMC genomics · 2024Article
- Spatial Multi-Omics in Alzheimer's Disease: A Multi-Dimensional Approach to Understanding Pathology and Progression.Current issues in molecular biology · 2024Review
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7 authors.
Funding
Abstract
The molecular changes that occur with the progression of Alzheimer's disease (AD) are well known, but an understanding of the spatiotemporal heterogeneity of changes in the brain is lacking. Here, we investigated the spatially resolved transcriptome in a 5XFAD AD model at different ages to understand regional changes at the molecular level. Spatially resolved transcriptomic data were obtained from 5XFAD AD models and age-matched control mice. Differentially expressed genes were identified using spots clustered by anatomical structures. Gene signatures of activation of microglia and astrocytes were calculated and mapped on the spatially resolved transcriptomic data. We identified early alterations in the white matter (WM) of the AD model before the definite accumulation of amyloid plaques in the gray matter (GM). Changes in the early stage of the disease involved primarily glial cell activation in the WM, whereas the changes in the later stage of pathology were prominent in the GM. We confirmed that disease-associated microglia (DAM) and astrocyte (DAA) signatures also showed initial changes in WM and that activation spreads to GM. Trajectory inference using microglial gene sets revealed the subdivision of DAMs with different spatial patterns. Taken together, these results help to understand the spatiotemporal changes associated with reactive glial cells as a major pathophysiological characteristic of AD. The heterogeneous spatial molecular changes apply to identifying diagnostic and therapeutic targets caused by amyloid accumulation in AD.
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