APOE4 gene and associated risk for Alzheimer's disease | Dale Bredesen
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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.
A neurodegenerative disorder characterized by progressive memory loss, spatial disorientation, cognitive dysfunction, and behavioral changes. The pathological hallmarks of Alzheimer's disease include amyloid-beta plaques, tau tangles, and reduced brain glucose uptake. Most cases of Alzheimer's disease do not run in families and are described as "sporadic." The primary risk factor for sporadic Alzheimer's disease is aging, with prevalence roughly doubling every five years after age 65. Roughly one-third of people aged 85 and older have Alzheimer's. The major genetic risk factor for Alzheimer's is a variant in the apolipoprotein E (APOE) gene called APOE4.
One of three common genetic variants of the APOE (apolipoprotein E) gene. The APOE4 allele, which is present in approximately 10-15% of people, increases the risk of developing Alzheimer's disease and lowers the age of onset. Having one copy of E4 increases risk 2- to 3-fold, while having two copies increases risk as much as 15-fold.
A battery of tests focused on a number of biomarkers that gauge a person’s risk for and status of cognitive decline. The baseline cognoscopy is also a component of the ReCODE program, which stands for reversal of cognitive decline, a program created by and based off the research of Dr. Dale Bredesen.
A general term referring to cognitive decline that interferes with normal daily living. Dementia commonly occurs in older age and is characterized by progressive loss of memory, executive function, and reasoning. Approximately 70 percent of all dementia cases are due to Alzheimer’s disease.
An amino acid present in the blood. Homocysteine is produced during the metabolism of methionine. Abnormalities in methionine metabolism can lead to elevated homocysteine levels, a condition called hyperhomocysteinemia. Elevated homocysteine levels can contribute to arterial plaque formation and increase the risk of clot formation. Some evidence suggests that elevated homocysteine levels double the risk of developing Alzheimer’s disease. Homocysteine levels vary according to dietary intake, with highest levels associated with consumption of animal protein. Variants in the genes that encode for the enzymes that metabolize homocysteine, specifically MTHFR, or methylenetetrahydrofolate reductase, markedly increase the risk of developing a wide array of diseases, including cardiovascular disease, Alzheimer’s disease, and cancer. High intake of dietary folate (present in leafy greens and other fruits and vegetables) can modulate the harmful effects associated with MTHFR.
A critical element of the body’s immune response. Inflammation occurs when the body is exposed to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective response that involves immune cells, cell-signaling proteins, and pro-inflammatory factors. Acute inflammation occurs after minor injuries or infections and is characterized by local redness, swelling, or fever. Chronic inflammation occurs on the cellular level in response to toxins or other stressors and is often “invisible.” It plays a key role in the development of many chronic diseases, including cancer, cardiovascular disease, and diabetes.
A biochemical process involving the addition or subtraction of a methyl group (CH3) to another chemical group. In epigenetics, a methyl group is added to an amino acid in a histone tail on DNA, altering the activity of the DNA segment without changing its sequence. Under- and over-methylation are referred to as hypomethylation and hypermethylation, respectively.
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