Apolipoprotein E (APOE), a lipoprotein produced in the liver and the brain, plays key roles in fat metabolism. Approximately 25 percent of people in the United States – roughly 75 million people – carry a genetic variant of this lipoprotein called APOE4, which is associated with higher circulating levels of LDL cholesterol and an increased risk for Alzheimer's disease. In this clip, Dr. Dale Bredesen describes the risks associated with APOE4 and identifies strategies for mitigating that risk.
Dale: Yeah, so, Apolipoprotein E is a really fascinating story, and of course, Professor Robert Mahley discovered this decades ago, and it has turned out to be the most important genetic risk factor for Alzheimer's disease. Seventy-five million Americans have a single copy of ApoE4. And when I say that what I mean by that is, everybody has two copies of either 2, 3, or 4, and the most common one is ApoE3. So it's common for people to be a 3,3 as an example. However, about a quarter of the population, so about 75 million Americans have one copy of ApoE4, and that's actually the primordial one. It's the one that was present for about 96% of hominid evolution.
If you look at a chimp, for example, it does not have ApoE4 but the hominids do, and still about 25% of the population today. Then about seven million Americans have two copies, so they're homozygous for ApoE4. Now, if you have zero copies, so if you're, for example, a 3,3 your overall lifetime risk for Alzheimer's is about 9%, so not a terribly common disease but not zero. On the other hand, if you have a single copy of ApoE4 your lifetime risk is about 30% or so. If you have two copies, if you're homozygous, your lifetime risk is over 50%, and in some studies as high as 90%. So most likely you will get it. And of course, the vast majority of people don't know.
Now, in the past people said, "Don't check because there's nothing you can do about it," and that has completely changed. So there is a tremendous amount, and the reality is Alzheimer's should be a rare disease. It should essentially decrease to a very low level with the current generation. If everybody gets checked, we recommend that everybody 45 or over get a cognoscopy, it's a silly term but it's easy to remember. Everybody knows when you hit 50 you should get a colonoscopy, and if you hit 45 or over you should be getting a cognoscopy. You should be doing some testing and see where you stand, what are your risk factors, are you ApoE4 positive, do you have high homocysteine, methylation issues, inflammatory issues, nutrient issues, toxin issues, all these things, because they can all be addressed, and we can decrease the overall global burden of dementia.
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