Lifestyle factors that affect Alzheimer’s risk for APOE4 carriers | Peter Attia
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Diet and lifestyle play considerable roles in the risk of developing Alzheimer's disease, particularly in people who carry an APOE4 gene variant. Consuming alcohol may be more detrimental to those with an APOE4 allele as they are less able to repair the damage inflicted on the brain. In addition, eating refined carbohydrates and added sugars contributes to the inflammatory molecules that can cross the blood-brain barrier. In this clip, Dr. Peter Attia and Dr. Rhonda Patrick discuss the unique dietary and lifestyle considerations for carriers of the APOE4 gene variant.
Rhonda: There's a huge, huge component for lifestyle in risk for Alzheimer's disease, particularly with having an ApoE4 allele, and that's where I've become obsessed. You know, I've been looking at mechanism but also looking at the epi studies. Looking at epidemiology, you see certain lifestyle factors for example, drinking. If you're drinking and you are ApoE4 because you're inducing damage that you can't repair as well, you're going to fare worse. You know, so anything that's going to damage your body worse, anything that's going to create inflammation...refined carbohydrate, eating a bunch of refined carbohydrates, a bunch of sodas with added sugars. Like, all this stuff that's terrible for you, that's not whole food, that's not something that's nutritious, that's going to cause inflammation. Inflammatory molecules get across the blood-brain barrier.
You know, so blah, blah, blah, and all this damage can continue to occur. So obviously, diet, lifestyle play a very important role in your Alzheimer's risk. And I think that understanding the biology of what ApoE4 is doing because now there's research, a lot of it coming out of UCSF Gladstone Institute showing that in addition to a loss of function with the ApoE4 allele, there's also a dominant negative effect. So apparently, the ApoE4, there's this 2-amino-acid substitution and structurally, if you look at the structure of the protein, it starts to get cleaved. And so it itself starts to accumulate these, like, aggregates that then you get more activated microglia and it keeps, like, spiraling out this whole inflammatory process in the brain. So there's also this dominant negative effect that's going on that's interesting. And you want to understand that as well.
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 highly selective semi-permeable barrier in the brain made up of endothelial cells connected by tight junctions. The blood-brain barrier separates the circulating blood from the brain's extracellular fluid in the central nervous system. Whereas water, lipid-soluble molecules, and some gases can pass through the blood-brain barrier via passive diffusion, molecules such as glucose and amino acids that are crucial to neural function enter via selective transport. The barrier prevents the entry of lipophilic substances that may be neurotoxic via an active transport mechanism.
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.
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