Matt Kelly explains why APOE4 carriers face 10 to 15 times higher Alzheimer's risk. He breaks down the genetic markers involved and describes a theory linking APOE4 to disrupted insulin binding in the brain, sometimes called type 3 diabetes.
In the intervening years, we discover, well, there's different subcategories of ApoE, and specifically ApoE4. We now can look at your genetics, and if you have ApoE4 genetic problems, SNPs, etc., you have 10 to 15 times increase in your probability of getting Alzheimer's disease. Well, how does ApoE4 tell us, not 1, not 2, not 3, that we might have more likelihood of Alzheimer's disease? And the reason that ApoE4 might inform us of that is that ApoE4 has a specific activity in the brain for interfacing with the insulin binding site. So this goes back to type 3 diabetes. And so in the rest of our body, ApoE does a lot of work at the liver. In the brain, ApoE4 is sort of responsible for a bunch of things, but one is sort of maintaining the insulin binding site in the brain.
