There continues to be strong interest in whether a mechanistic relationship exists between APOE and brain parenchymal tau that is independent of amyloid, as has been suggested by analyses of primary tauopathies and selected studies using cellular and animal model systems (Shi et al., 2017; Zhao et al., 2018; Wadhwani et al., 2019). This evidence concerns the gene APOE and tauopathy.