Spatially resolved transcriptomics reveals gene signatures underlying the vulnerability of human middle temporal gyrus in Alzheimer's disease

Abstract Human middle temporal gyrus (MTG) is a vulnerable brain region in early Alzheimer's disease (AD); however, little is known about the molecular mechanisms underlying this regional vulnerability. Here we use the 10x Visium platform to define the spatial topography of gene expression in the MTG from both early AD and control cases. We identify differentially expressed genes (DEGs) and enriched pathways that may contribute to the layer-specific vulnerability of AD pathology. Also, gene co-expression analyses reveal four gene modules, which significantly change their co-expression patterns in the presence of variations of AD pathology. Furthermore, we validate the changes of key representative DEGs that are associated with AD pathology using single-molecule fluorescent in situ hybridization. In summary, we provide a rich resource for the spatial transcriptomic profile of the human MTG, which will contribute to our understanding of the complex architecture and AD pathology of this vulnerable brain region.