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.