Interestingly, the AD-risk factor ApoE4 actually prevents this protective effect by sequestering the ApoE receptors along with other synaptic receptors in the endosome (Chen et al., 2010), and postnatal loss of Reelin exacerbates the cognitive deficits in AD mouse model (Lane-Donovan et al., 2015). Here, APOE is linked to Alzheimer disease.