Brain cell transcriptomics in vulnerable and resilient regions in Alzheimer’s Disease brains

• DOI: 10.1002/alz.091719
• Publication Date: 2025-01-09T12:18:01Z
• Authors: Gabriela Mantovan...; Giovanna Carello‐...; Christian Limberger; Rodrigo Sebben Paes; Marco De Bastiani; Eduardo R. Zimmer

Abstract Background Neurodegeneration is a major pathological feature of Alzheimer’s disease (AD). During this process, it known that not only neurons are affected but also glial cells. However, the biological mechanisms driving brain cellular vulnerability and resilience to neurodegeneration in AD remain elusive. Thus, we aimed investigate transcriptomic profile cell types vulnerable resilient regions. Method We searched microarray datasets Gene Expression Omnibus repository for available transcriptomics (hippocampus entorhinal cortex) (cerebellum) postmortem The data was downloaded using GEOquery package. performed gene expression deconvolution with Population‐Specific Analysis (PSEA) obtain differentially expressed genes (DEGs) specific neurons, astrocytes, microglia, oligodendrocytes, endothelial cells (FDR‐adjusted p‐value < 0.05). then executed functional enrichment analysis Ontology (GO) Biological Processes (GOBP) terms (clusterProfiler package). All analyses were done R. Result included eight GSEs regions, comprising 165 cognitively unimpaired (CU) 182 individuals, two (123 CU, 179 AD). PSEA revealed an increased percentage DEGs oligodendrocytes regions when compared (Figure 1A). By contrast, among remained similar 1B). Interestingly, presented more related than ones 1C). Microglia type most GOBPs number while astrocytes had one (Table 1). Table 2 shows Conclusion demonstrate presenting higher Other exhibit both Regarding GOBPs, all show enriched regions; however, do any terms. These findings suggest possess exceptional ability adapt trait observed