Tau accumulation induces microglial state alterations in Alzheimer’s disease model mice (Spatial Transcriptomics)

Unique microglial states have been identified in Alzheimer’s disease (AD) model mice and postmortem AD brains. Although it has been well documented that amyloid-β accumulation induces the alteration of microglial states, the relationship between tau pathology and microglial states remains incompletely understood because of a lack of suitable AD models. In the present study, we generated a novel AD model mouse by the intracerebral administration of tau purified from human brains with primary age-related tauopathy into AppNL-G-F/MAPT double knock-in (dKI) mice. Cellular mRNA in the tau-injected dKI (Tau-dKI) brain was captured on thousands of spots (each 55 μm in diameter) using oligonucleotides with spatial barcodes.