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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.<\/jats:p>","DOI":"10.3390\/ijms27115020","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"5020","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Multi-Dimensional Transcriptomics Reveals the Prominent Role of Neuroinflammation in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"27","author":[{"given":"Xingyu","family":"Wang","sequence":"first","affiliation":[{"name":"Hwamei College of Life and Health Sciences, Zhejiang Wanli University, Ningbo 315100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7811-4890","authenticated-orcid":false,"given":"Zhouting","family":"Rong","sequence":"additional","affiliation":[{"name":"Hwamei College of Life and Health Sciences, Zhejiang Wanli University, Ningbo 315100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5058-5735","authenticated-orcid":false,"given":"Feng","family":"Xue","sequence":"additional","affiliation":[{"name":"Hwamei College of Life and Health Sciences, Zhejiang Wanli University, Ningbo 315100, China"},{"name":"Zhejiang Key Laboratory of Intelligent Food Logistic and Processing, Yuyao Innovation Institute, Zhejiang Wanli University, Ningbo 315400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1038\/s41586-024-07606-7","article-title":"Single-cell multiregion dissection of Alzheimer\u2019s disease","volume":"632","author":"Mathys","year":"2024","journal-title":"Nature"},{"key":"ref_2","unstructured":"World Health Organization (2021). 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