APOE and Alzheimer disease: The ApoE4 isoform, which is regarded as genetic risk factor of AD, exhibited poor ability in regulating Aβ clearance, therefore Aβ aggregation accelerated in the brain which boosted age-dependent cognitive impairment while the other two isoforms promoted effective removal of Aβ peptides from brain and reduced the risk of cognitive decline (Jiang et al., 2008; Liu et al., 2013).