Alzheimer disease (AD) is a devastating neurological disease associated with progressive loss of mental skills and cognitive and physical functions whose etiology is not completely understood. Here, our goal was to simultaneously uncover novel and known molecular targets in the structured layers of the hippocampus and olfactory bulbs that may contribute to early hippocampal synaptic deficits and olfactory dysfunction in AD mice. Spatially resolved transcriptomics was used to identify high-confidence genes that were differentially regulated in AD mice relative to controls. A diverse set of genes that modulate stress responses and transcription were predominant in both hippocampi and olfactory bulbs. Notably, we identify Bok, implicated in mitochondrial physiology and cell death, as a spatially downregulated gene in the hippocampus of mouse and human AD brains. In summary, we provide a rich resource of spatially differentially expressed genes, which may contribute to understanding AD pathology.

阿尔茨海默氏病（AD）是一种破坏性神经病，与精神技能的逐步丧失以及认知和身体功能的丧失有关，其病因尚未得到完全了解。在这里，我们的目标是在海马和嗅球的结构层中同时发现新颖和已知的分子靶标，这些分子靶标可能会导致AD小鼠早期海马突触缺陷和嗅觉功能障碍。使用空间分辨的转录组学来鉴定与对照相比在AD小鼠中差异调节的高可信度基因。在海马和嗅球中，调节应激反应和转录的多种基因占主导。值得注意的是，我们确定Bok与线粒体生理和细胞死亡有关，作为小鼠和人类AD脑海马中空间下调的基因。总之，我们提供了空间差异表达基因的丰富资源，这可能有助于理解AD病理。