LRP8 and Alzheimer disease: 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).