APOE and Alzheimer disease: The proposed mechanism(s) through which APOE4 increases AD risk are multifactorial, including both amyloid-β (Aβ)-dependent effects, i.e. modulation of Aβ levels, aggregation, neurotoxicity and neuroinflammation, and Aβ-independent effects, i.e. neuronal development, glucose metabolism, brain activity and lipid metabolism (reviewed in[3]).