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If you've been consistent with daily dosing, proper reconstitution, and refrigerated storage, and still see zero change at 16 weeks, the issue is likely absorption or individual receptor sensitivity rather than insufficient dose

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Female 5xFAD mice that express human APOE4 (E4FAD) exhibit increased anxiety-like behavior relative to E3FAD, and ovariectomy (OVX) in E3FAD mice increases anxiety to a similar level to intact and OVXed E4FAD mice, suggesting a protective role of ovarian hormones against anxiety-like phenotypes in E3FAD but not E4FAD mice (Taxier et al., 2022)