APOE and Alzheimer disease: Ageing is a prominent risk factor for the development of the sporadic form of Alzheimer’s disease, which accounts for ∼95% of all cases.22,23 Mounting evidence revealed that LRP1 expression declines in brain blood vessels and parenchyma during normal ageing in rodents and humans and is further reduced in Alzheimer’s disease individuals.11,24–26 Moreover, validated genetic risk factors for Alzheimer’s disease, including ApoE E4 allele27 and the gene encoding for phosphatidylinositol-binding clathrin assembly (PICALM),28 are linked to diminished clearance of Aβ via LRP1.