APOE4 and the history of human disease

Apolipoprotein E, discovered in 1973, is derived from a polymorphic gene called ApoE that encodes for a signaling protein on a class of fatty proteins that primarily carry cholesterol and other molecules around the body. We find ApoE primarily on VLDL, very low-density lipoproteins and HDL, High density lipoproteins. It primarily helps to shuttle cholesterol from the periphery of the body back to the liver. ApoE proteins are also involved in neuronal signaling, neuroinflammation and glucose metabolism making them especially critical for brain activity. This is becoming a critical part of the story for understanding dementia and neurodegeneration. (Williams T. 2020) ApoE is most famous for an isoform, APOE4/4, being highly associated with Alzheimer’s dementia in modernity. Unfortunately, as we do with many things in medicine, we have been focused on this genetic protein variant as a net negative in humans because we look at things as black and white. Either good or bad. A binary choice. Rubish! .....

Enjoy,
Dr. M