Single nucleus RNA-seq of brain regions showing high-low Abeta plaque pathology in a mouse model of Alzheimer's disease

Alzheimer's Disease (AD) pathology and amyloid-beta plaque deposition progress slowly in the cerebellum compared to other regions, while the entorhinal cortex (EC) is one of the most vulnerable regions. Using a knock-in mouse model (App KI) of preclinical AD, we show that within the cerebellum, the deep cerebellar nuclei (DCN) show particularly low Aβ plaque accumulation. To identify factors that might underlie differences in the progression of AD-associated neuropathology across regions, we profiled gene expression in single nuclei (snRNAseq) across all celltypes in the DCN and EC of wild-type and App KI male mice at age 7 months. EC and DCN from N=2 wild-type and AppNL-G-F knock-in mice were dissected. Single nuclei were then isolated by sucrose cushion centrifugation and sequenced using the 10X droplet-based method.阿尔茨海默病（AD）的病理进程与β淀粉样斑块沉积在小脑中的进展速度相较于其他脑区更为缓慢，而内嗅皮层（EC）则是最易受影响的脑区之一。本研究使用临床前阿尔茨海默病的基因敲入小鼠模型（App KI），证实小脑深部核团（DCN）的Aβ斑块沉积水平尤其低下。为了明确可能导致不同脑区AD相关神经病理进展差异的关键因素，我们对7月龄野生型与App KI雄性小鼠的小脑深部核团及内嗅皮层中所有细胞类型的单细胞核进行了转录组测序（snRNAseq）。本实验共解剖了N=2只野生型小鼠与AppNL-G-F基因敲入小鼠的内嗅皮层与小脑深部核团，随后通过蔗糖密度垫离心法分离单细胞核，并采用10X液滴测序技术完成测序。