APOE and tauopathy: It has been reported that, following its cellular release, HMGB1 acts as a pro-neuroinflammatory DAMP that induces gliosis.44,60 To determine the importance of released HMGB1 in triggering acute gliosis in APOE4-related tauopathy, 10-month-old wild-type mice received a unilateral injection of hippocampal ISF collected from 10-month-old PS19-E4 mice that either was enriched with high concentrations of HMGB1 (fractions 19–22 in Figure 2D) or had undetectable levels of HMGB1 as a control (fractions 3–7 in Figure 2D).