APOE and Alzheimer disease: However, a number of studies in mice have shown that APOE4 alone can influence AD progression by affecting numerous, Aβ-independent processes including impaired learning behaviors, reduced synaptic plasticity and neurogenesis, increased neuroinflammation, neurotoxicity of fragmented APOE4, impaired mitochondrial function, and increased tauopathy (Yadong Huang 2011; Yamazaki et al. 2016).