SnRNA-seq analysis of hippocampus in TAFE3 and TAFE4 mice

Tau-mediated neurodegeneration (TN) is a hallmark of Alzheimer's disease. Primary tauopathies are characterized by pathological tau accumulation and neuronal and synaptic loss. Studies have shown that ApoE-mediated neuroinflammation is involved in progression of TN and emerging evidence suggests that the gut microbiota regulates neuroinflammation in an APOE-genotype dependent manner. However, there is no evidence showing a causal link of the microbiota to TN. Therefore, we have characterized a genetically engineered mouse model of tauopathy expressing human ApoE isoforms, reared under germ-free conditions or after perturbation of their gut microbiota with antibiotics. Both these manipulations produced a striking reduction of gliosis, taupathology, and neurodegeneration in a sex- and ApoE isoform-dependent manner. The findings reveal mechanistic and translationally relevant interrelationships between the microbiota, neuroinflammation, and TN." Overall design: Droplet-based 3? end massively parallel single-cell RNA sequencing was performed by isolating single nuclei from flash-frozen mouse brains through sucrose gradient and libraries were prepared using Chromium Single Cell 5? Reagent Kits according to manufacturer's protocol (10x Genomics). The generated scRNAseq libraries were sequenced using Illumina sequencers.