APOE and Alzheimer disease: While the exact mechanism by which different APOE isoforms contribute to AD pathophysiology remains to be elucidated, human and animal studies have consistently shown that APOE4 is linked to increased deposition of amyloid beta (Aβ) plaques in the brain [18, 20–25], impaired intracellular lysosomal degradation of Aβ [26–29], and increased levels of neuroinflammation [30–33].