To investigate whether APOE4 promotes HMGB1 translocation in the absence of tauopathy, we analyzed human APOE (E) knockin mice that lacked human mutant Tau-P301S.49 Immunostaining for HMGB1 in 10-month-old mice showed that the majority of HMGB1 remained localized within the nucleus of hippocampal neurons in both E4 and E3 mice (Figures S3A–S3D). Here, MAPT is linked to tauopathy.