Several studies have shown the isoform-specific APOE involvement in the AD pathogenesis and onset of the disease, reporting that APOE ε4 allele shows increased levels of amyloid aggregation, lower levels of amyloid clearance due to a non-optimal lipidation state of APOE4 and affects the BBB permeability [22,23,24]. Here, APOE is linked to Alzheimer disease.