1. Stereo-seq of the prefrontal cortex in aging and Alzheimer’s disease
- Author
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Yun Gong, Mohammad Haeri, Xiao Zhang, Yisu Li, Anqi Liu, Di Wu, Qilei Zhang, S. Michal Jazwinski, Xiang Zhou, Xiaoying Wang, Kai Zhang, Lindong Jiang, Yi-Ping Chen, Xiaoxin Yan, Russell H. Swerdlow, Hui Shen, and Hong-Wen Deng more...
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Science - Abstract
Abstract Aging increases the risk for Alzheimer’s disease (AD), driving pathological changes like amyloid-β (Aβ) buildup, inflammation, and oxidative stress, especially in the prefrontal cortex (PFC). We present the first subcellular-resolution spatial transcriptome atlas of the human prefrontal cortex (PFC), generated with Stereo-seq from six male AD cases at varying neuropathological stages and six age-matched male controls. Our analyses revealed distinct transcriptional alterations across PFC layers, highlighted disruptions in laminar structure, and exposed AD-related shifts in layer-to-layer and cell-cell interactions. Notably, we identified genes highly upregulated in stressed neurons and nearby glial cells, where AD diminished stress-response interactions that promote Aβ clearance. Further, cell-type-specific co-expression analysis highlighted three neuronal modules linked to neuroprotection, protein dephosphorylation, and Aβ regulation, with all modules downregulated as AD progresses. We identified ZNF460 as a transcription factor regulating these modules, offering a potential therapeutic target. In summary, this spatial transcriptome atlas provides valuable insight into AD’s molecular mechanisms. more...
- Published
- 2025
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