APOE and Alzheimer disease: Mechanistically, APOE4 contributes to AD pathogenesis evidenced by enhanced amyloid-β aggregation (Yamazaki et al., 2019, Verghese et al., 2013, Kanekiyo et al., 2014), exacerbated tau pathology (Shi et al., 2017), impaired glucose metabolism and lipid homeostasis (Wu et al., 2018, Qi et al., 2021, Zhao et al., 2017), altered microglial response (Kanekiyo et al., 2014, Fernandez et al., 2019), reduced synaptic integrity and plasticity (Dumanis et al., 2009, Ji et al., 2003, Klein et al., 2010), and disrupted cerebrovascular integrity and function (Koizumi et al., 2018, Halliday et al., 2016).