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Last-Initial3927 t1_j4cq7mj wrote

Reply to comment by LizzieButtons in Alzheimer’s tied to cholesterol, abnormal nerve insulation by D-R-AZ

I think your question contains a great teaching point about genetics. I prefer to think about genetics as a repertoire like a toolbox that a carpenter brings to a job. What tools are used is somewhat dictated by what’s in the box but if he is say sawing a plank of wood then he’s not going to reach for the hammer. The cell is trying to make similar contextual decisions all of the time. Diet and exercise may dramatically alter both gene expression and the effect of a product secreted into a vastly different environment.

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LizzieButtons t1_j4crn6n wrote

> Diet and exercise may dramatically alter both gene expression and the effect of a product secreted into a vastly different environment.

This is the basic idea I’m interested in. So there is evidence that diet and exercise can affect the expression of genes like this? Maybe not for this specific gene but do you know of an example where a genetic defect is controlled or put in remission without other therapies?

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fitandhealthyguy t1_j4edhaq wrote

It’s not a matter of expression of the gene. ApoE transports and helps to dispose of cholesterol. The ApoE4 subtype is not good at transporting and disposing of cholesterol so cholesterol builds up where it shouldn’t be. Reducing cholesterol through diet and exercise means less cholesterol for ApoE to act on - the ApoE4 is still defective, but there is less cholesterol to gum up the works.

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LizzieButtons t1_j4eiw6x wrote

Cholesterol builds up where it shouldn’t AND does go where it is needed to make nerve sheath, if I’m reading correctly. So isn’t something still needed to redirect the cholesterol where it needs to go, not just to reduce overall cholesterol?

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fitandhealthyguy t1_j4fmtsp wrote

It is a little complicated. ApoE transports cholesterol. The different isoforms have different abilities to bind cholesterol. ApoE2 is best, then ApoE3 with ApoE4 the worse but it still has some ability to bind and transport cholesterol. When cholesterol levels are low on the blood, ApoE4 might do an ok job but when cholesterol levels are higher, it can’t keep up. Also consider that there are heterozygotes (ApoE3/ApoE4) that fair better and homozygotes (ApoE4/ApoE4) that have the highest risk.

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