Recently, it was demonstrated that the association of APOE-ε4 with lower late-life global cognitive scores was mediated by a higher burden of AD-pathology, as well as the presence of CAA, LBD, and TDP-43 in 1,671 participants, while cerebrovascular lesions were not mediators of the association between APOE alleles and cognitive function  [19]. This evidence concerns the gene TARDBP and Alzheimer disease.