Interestingly, of all pathological correlations made in PS19-fE4 mice, the coverage area of CD68+ activated microglia had the strongest negative correlation with hippocampal volume (Fig. 6f), suggesting that the extent of microglial activation is the strongest indicator and potential contributor to APOE4-promoted hippocampal degeneration in tauopathy. This evidence concerns the gene APOE and tauopathy.