APOE

APOE is involved in lipid metabolism. Mice without APOE show dysregulations in lipid metabolism, having higher plasma cholesterol levels and developing arterial lesions, displaying DNA oxidative stress at a hepatic level, and presenting severe atherosclerosis and cutaneous xanthomatosis. They also have a significantly shorter lifespan than wild-type. Neurodegeneration has also been reported in APOE-null mice. Several polymorphisms in the human APOE gene have been associated with diseases, such as increased risk of myocardial infarction and Alzheimer’s disease. Polymorphisms in APOE have been linked to human longevity. There are four isoforms of APOE in humans. In Alzheimer’s disease the ApoE2 isoform is protective and the ApoE4 isoform is causative and stimulates amyloid beta production. ApoE4 also exacerbates tauopathy in mouse models of Alzheimer’s disease and ApoE4 knock-in mice show significantly higher levels of tau in the brain. Despite its association with age-related disease the ApoE4 isoform is the second most common after the ApoE3 isoform and is the ancestral form of APOE. Clearly, APOE has an impact on various age-related diseases, such as atherosclerosis and neurodegeneration, but its overall impact on the human ageing process remains to be determined.