Neuropathological evidence that the association between APOE‐e4 genotype and higher medial temporal lobe tau burden is mediated by higher local amyloid‐β levels

Evidence from previous PET imaging studies suggests that increased neocortical tau seen in APOE‐ε4 carriers can be explained by the higher levels of neocortical amyloid‐β (Aβ) pathology also seen in this group. However, these studies also suggest an amyloid‐independent association between APOE‐ε4 and medial temporal lobe (MTL) tau. Using neuropathological data, we investigated whether amyloid‐β in the MTL, which is difficult to accurately measure with PET, may fully mediate the association between APOE‐ε4 carriership and MTL tau burden.