Spatial transcriptome study on human prefrontal cortex

In this study, we employed a cutting-edge spatial transcriptome platform, SpaTial Enhanced Resolution Omics-sequencing (Stereo-seq), to generate the first comprehensive, subcellular resolution spatial transcriptome atlas of the human prefrontal cortex from six AD cases at various neuropathological stages and six age, sex, and ethnicity matched controls. Our analyses revealed distinct transcriptional alterations across six neocortex layers, highlighted the AD-associated disruptions in laminar architecture, and identified changes in layer-to-layer interactions as AD progresses. Further, throughout the progression from NA to various stages of AD, we discovered specific genes that were significantly upregulated in neurons experiencing high stress and in nearby non-neuronal cells, compared to cells distant from the source of stress.