*Geek Box: ApoE-4

*Geek Box: ApoE-4

Apolipoprotein E [ApoE] is a protein expressed in tissues throughout the body, but with particularly high expression in the liver and in the brain. The e4 variant of the ApoE gene [ApoE-e4] is strongly associated with Alzheimer’s Disease. The mechanisms identified to date is the influence of this gene on metabolism of amyloid-beta [AB] protein in the brain. The high metabolic activity – and therefore waste generation – by the brain results in the production of amyloid-B precursor protein [APP]. APP can be metabolised through a number of pathways: the gamma-secretase pathway is strongly implicated in the build up of AB and plaque formation in the brain. Mechanistically, high cholesterol levels contribute to this abnormal processing of AB protein. The ApoE-e4 genetic variant may increase risk for Alzheimer’s by resulted in disordered AB metabolism in the brain, either through impaired clearance of AB or through influencing disordered cholesterol metabolism [the two may interact]. While the mechanistic processes remain to be fully elucidated, there is compelling evidence supporting a significantly increased Alzheimer’s risk with the ApoE-e4 genetic variant. Those with this variant are generally advised to follow a diet very low in saturated fat, lower in total fat, and low in dietary cholesterol.