HMGB1 and tauopathy: Although it was previously unclear how APOE4 induces neuroinflammation, we show that APOE4 has a compelling effect of promoting the intraneuronal translocation and release of HMGB1, which is a key pro-neuroinflammatory DAMP in the brain.36,60 Interestingly and importantly, pharmacological inhibition of HMGB1 intracellular translocation and release reduces not only gliosis, but also Tau pathology in APOE4 tauopathy mice.