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Peer-reviewedCC BYInternational Journal of Molecular Sciences

Multi-Dimensional Transcriptomics Reveals the Prominent Role of Neuroinflammation in Alzheimer’s Disease

Abstract

Alzheimer's Disease (AD), the most common form of dementia, is pathologically defined by extracellular beta-amyloid (Aβ) plaques and intraneuronal neurofibrillary tangles (NFTs), accompanied by chronic neuroinflammation. Recent advances in single-cell RNA sequencing (scRNA-seq/snRNA-seq) and spatial transcriptomics have provided unprecedented resolution for unraveling the cellular and molecular landscape of neuroinflammation in AD. While scRNA-seq enables high-throughput profiling of cellular heterogeneity across brain regions, spatial transcriptomics preserves tissue architecture to map cell-type-specific gene expression within its anatomical context. This review synthesizes the neuroinflammatory mechanisms of AD, outlines the technical evolution and comparative capabilities of single-cell and spatial omics platforms, including resolution, throughput, and compatibility with multiple sample types, and critically evaluates findings from studies in both animal models and human brain tissues. These approaches have revealed state-specific transitions in microglia and astrocytes, including shifts in transcriptional programs, metabolic reprogramming, and pro-inflammatory polarization across disease stages. Notably, spatial transcriptomic analyses demonstrate pronounced regional heterogeneity: periplaque microenvironments exhibit distinct immune-cell compositions and gene expression signatures. Collectively, these omics technologies are redefining the cellular basis of AD progression and hold the potential to impact the discovery of early diagnostic biomarkers and precision therapeutic targets.

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BibTeX
@article{wang2026multidimensional,
  title = {{Multi-Dimensional Transcriptomics Reveals the Prominent Role of Neuroinflammation in Alzheimer’s Disease}},
  author = {Xingyu Wang and Zhouting Rong and Feng Xue},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = jun,
  doi = {10.3390/ijms27115020},
  url = {https://doi.org/10.3390/ijms27115020},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Multi-Dimensional Transcriptomics Reveals the Prominent Role of Neuroinflammation in Alzheimer’s Disease
AU  - Xingyu Wang
AU  - Zhouting Rong
AU  - Feng Xue
PY  - 2026
DA  - 2026/06/02
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27115020
UR  - https://doi.org/10.3390/ijms27115020
AB  - Alzheimer's Disease (AD), the most common form of dementia, is pathologically defined by extracellular beta-amyloid (Aβ) plaques and intraneuronal neurofibrillary tangles (NFTs), accompanied by chronic neuroinflammation. Recent advances in single-cell RNA sequencing (scRNA-seq/snRNA-seq) and spatial transcriptomics have provided unprecedented resolution for unraveling the cellular and molecular landscape of neuroinflammation in AD. While scRNA-seq enables high-throughput profiling of cellular heterogeneity across brain regions, spatial transcriptomics preserves tissue architecture to map cell-type-specific gene expression within its anatomical context. This review synthesizes the neuroinflammatory mechanisms of AD, outlines the technical evolution and comparative capabilities of single-cell and spatial omics platforms, including resolution, throughput, and compatibility with multiple sample types, and critically evaluates findings from studies in both animal models and human brain tissues. These approaches have revealed state-specific transitions in microglia and astrocytes, including shifts in transcriptional programs, metabolic reprogramming, and pro-inflammatory polarization across disease stages. Notably, spatial transcriptomic analyses demonstrate pronounced regional heterogeneity: periplaque microenvironments exhibit distinct immune-cell compositions and gene expression signatures. Collectively, these omics technologies are redefining the cellular basis of AD progression and hold the potential to impact the discovery of early diagnostic biomarkers and precision therapeutic targets.
SN  - 1422-0067
SN  - 1661-6596
ER  -