Notably, the ApoE4 isoform, a genetic risk factor for AD, reduces the surface expression of ApoER2 (Chen et al., 2010), whereas a gain-of-function mutation in this Reelin pathway has been implicated in sparing the EC from tau pathology and supporting cognitive resilience despite otherwise widespread neuropathology (Lopera et al., 2023). Here, RELN is linked to Alzheimer disease.