Microglial state changes in response to LM11A‐31 promote recovery in a tauopathy mouse model of Alzheimer’s Disease

Tau pathologies in Alzheimer’s Disease (AD) contribute to neurodegeneration and synaptic degeneration via a variety of mechanisms. Neurotrophic signaling pathways present an avenue to counteract degenerative mechanisms via receptor modulating compounds, such as the p75NTR‐targeted small molecule LM11A‐31 (C31). Treatment with C31 in tauopathy models causes reductions in tau aggregation and microglial activation, restoration of synaptic plasticity, and prevention of synaptic spine loss. Using tauopathy model tauP301S mice (PS19), we examined the impact of long‐term dosing with C31 at the single‐cell transcriptional level to better understand the cell types and cellular mechanisms affected by treatment.