*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-4] is strongly associated with Alzheimer’s Disease. The mechanisms identified to date include the influence of this gene on metabolism of amyloid-beta 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-4 genetic variant may increase risk for Alzheimer’s by resulted in disordered amyloid-beta metabolism in the brain, either through impaired clearance of amyloid-beta 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-4 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.