Spatial transcriptomics in Alzheimer’s disease: Mapping cellular dysregulation in the brain microenvironment
1 Department of Internal Medicine (Consulting group), Obafemi Awolowo University Health Center, Ile-Ife, Nigeria.
2 Department of Biochemistry and Molecular Biology, Obafemi Awolowo University, Ile-Ife, Nigeria.
3 School of Medicine, St George's University, St. George's, Grenada.
4 Department of Biological Sciences, University of Camerino, Italy.
5 Department of Medicine and Surgery, Obafemi Awolowo University, Ife., Nigeria.
6 Department of Department of Community Medicine, College of Health and Well-Being, Kintampo, Ghana.
7 Department of Pharmacy, University of Benin, Benin city, Nigeria.
Review
International Journal of Biological and Pharmaceutical Sciences Archive, 2025, 10(01), 121-140
Article DOI: 10.53771/ijbpsa.2025.10.1.0064
Publication history:
Received on 24 June 2025; revised on 05 August; accepted on 08 August 2025
Abstract:
Alzheimer’s disease (AD), a leading cause of dementia, imposes a profound global burden, characterized by amyloid-β plaques, tau tangles, and progressive cognitive decline. Spatial transcriptomics (ST) has emerged as a transformative tool, mapping the brain’s complex microenvironment with unprecedented precision to reveal molecular underpinnings of AD pathology. This review explores ST’s role in dissecting the interactions of neurons, microglia, astrocytes, oligodendrocytes, and the neurovascular unit, uncovering spatially restricted dysregulation in regions like the hippocampus and cortex. By resolving plaque-induced inflammatory genes, synaptic loss markers, and vascular dysfunction, ST illuminates AD’s cellular heterogeneity across early/late stages and genetic/sporadic subtypes, offering a molecular blueprint for precision medicine. Open-access datasets, including GEO and comprehensive brain atlases, have accelerated these discoveries, fostering collaborative research into AD’s microenvironmental dynamics.ST’s clinical promise lies in its ability to inform therapeutic and diagnostic innovations. Biomarkers like microglial TREM2 and endothelial LRP1, identified through ST, guide patient stratification for anti-amyloid therapies and emerging microglial or vascular-targeted interventions, while enabling early detection through subtle entorhinal cortex changes. Despite challenges—resolution limits, data complexity, high costs, and ethical concerns—future directions, including AI-driven analysis, multi-omics integration, and novel platforms like STORM-seq, promise to overcome these hurdles. By bridging basic research and clinical practice, ST holds the potential to redefine AD management, offering hope for earlier diagnostics and personalized therapies to mitigate this devastating disease’s impact.
Keywords:
Spatial Transcriptomics; Alzheimer’s Disease; Brain Microenvironment; TREM2; Neurovascular Unit; Biomarker Discovery; Precision Medicine; AI Deconvolution
Full text article in PDF:
Copyright information:
Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0