The Key Genetic Factor in Alzheimer's: APOE4 Gene 🧬🧠

This episode is part of a live recording for our NEURO Academy community, and the topic of the discussion is the genetics of Alzheimer’s disease, in particular a deep dive into Apolipoprotein E4 or APOE4 gene, which is the most influential genetic risk factor associated with Late Onset Alzheimers Disease. We describe the evolutionary aspects of Apolipoproteins, how they are produced, how the different isoforms of apoe influence the different factors leading to AD, how it effects lipid metabolism and immune functions in the brain, and what is the latest evidence on the epigenetic of APOE4. Typically, the community members post their questions ahead of time and we structure the conversation in a way to address their questions, and also answer their questions during the recording.

Unraveling Alzheimer's Genetics: APOE4 Explained 🧬🧠 Join NEURO Academy's live recording as we dive into the influential APOE4 gene, a key genetic risk factor for Late Onset Alzheimer's Disease. #AlzheimersGenetics #APOE4 #NEUROAcademy #BrainHealth

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More episodes from The Brain Health Revolution Podcast:
-STROKE: Risk Factors & Epidemiology

- Ketogenic Diet and Alzheimer's - A Scientific Review

- Understanding Bruce Willis's Aphasia

- The Fiber Fueled Revolution with Dr. Will Bulsiewicz

- Alzheimer's Fraud - The Alleged Fabrication in Alzheimer's research and Articles. committee
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[kwikitti]

This is a very informative and reassuring discussion. I believe that for me, learning I'm homozygous apoE4 (over 5 years ago) has been beneficial, particularly after I learned that you have cared for 4/4's with advanced age who exhibit no signs of dementia. I feel very lucky that I can exercise vigorously, and I enjoy the challenges it brings, as well as enjoy following a WFPB diet since 2008. I have found the silver lining of my diagnosis: greater motivation to consistently make the lifestyle choices that are beneficial for basically all humans. Attending my 50th HS reunion last month, I realized that I was one of, if not the very healthiest of all my classmates. It felt so good to dance to the live band playing old rock tunes. I had so much energy and joy pouring out of me. It was my ideal way to celebrate my luck to be alive and thriving after 50 years. Thank you for your guidance and support!

[matkagrogan]

Isn’t that the risk of dementia among people with Apoe4 is much higher because of the milieu modern humans are living in? I mean low fat high-carb processed diet, eating 6-8 x a day etc? People with Apoe4 should all the more stick to ancestral diet

[bluecrewfan]

I'm 35 years old and carry a copy of ApoE 4. I run about 10-13 miles per week, minimize carbs and processed food, and I eat sardines and salmon at least 5 times a week. I also supplement with krill oil. I have not had a drink of alcohol in a while, though I'm not enthused about giving up wine. My question: what is the cost-benefit analysis for small amounts of alcohol? Is it even worth the risk for an ApoE 4 carrier?

[heldagsstrikk]

Thank you for explaining so clearly! Especially the details of what exercize actually does in the different areas of the body 👍😊

[Alice-oekd]

From what you both have said a daily allowance of 1 gram of DHA and 1 gram of Omega 3 per day would be a good amount - am I correct here. Since all of my immediate family died of dementia I am very interested in this topic. I already know that I have 2 copies of APOE4. Thank you so much for doing these videos.

[DanielOfAuburn]

❤ this is absolutely excellent! Thank you so much. Alzheimer's and Dementia are all over my family and I'm already seeing elevated levels of phosphorylated towel in my blood test. I am grateful that you guys took the time to put this video together.

[bijandanesh]

Very informative and motivating to adjust our lifestyle to minimise our risk of developing dementia and improving our overall health. Thank you for explains it all so clearly 🙏

[melanie.]

So thankful for this broadcast and the hope regarding how lifestyle impacts APOE4. There is so much fear surrounding this gene; it is so welcome to hear actual steps (i.e. physical exercise and reduction of saturated fats) and recommendations for what to do. Wondering whether increasing DHA supplementation or polyunsaturated fats as mentioned poses a risk of increasing cholesterol and what your thoughts are about this for the APOE4 individual? I am also wondering whether medication that focuses on the reduction of plaques and tangles is focusing on the wrong thing? It would also be great to hear your thoughts about BHRT in peri and menopausal women as well as pregnenolone for brain health.

[victoriajohnson]

I am just beginning to understand and research APOE4. I appreciate the help. My internal medicine Dr keeps throwing it at me verbally, but I had no idea what he was talking about. Family of diabetics, high cholesterol, and vascular dementia, and hypopnoea.
Dr pushing pills, and I'm trying to fix without prescriptions.

[iDalisMediaTV]

The most comprehensive explanation of the complexity of dementia therefore the difficulty in finding the root causes. Fascinating information regarding birds.

[nancieamethyst]

Perilla oil has some good studies on APOE4 knockout mice and also on elderly Japanese with very good effects on cognition. Perilla is extremely high in ALA.

[patangel]

Thank you, this was so relevant and informative.

[sk.n.]

This is anecdotal, but after having months of chronic fatigue syndrome (after 6 rounds of IVF drugs), the sauna was the only thing that helped me get better & how I regained my strenght.

[BlahBlahPoop]

34:00 The best quality data I have seen on data suggest that lowering overall saturated fat intake lowers LDL and heart disease risk because it lowers ApoB, which we no know without a doubt is the causal factor in atherosclerotic heart disease.

Independent of that, risk is further lowered by swapping out the saturated (and trans fat) for MUFA and PUFA. MUFA has a modest LDL lowering effect while PUFA has the greatest LDL lowering effect. They act like weaker statins on the LDL receptor, etc.

Fiber also lowers cholesterol levels by lowering cholesterol reabsorption throughout the day. Which is why small meals which include fiber throughout the day may also be better than one or two large meals with fiber. Plant polyphenols can also have a LDL lowering effect. But swapping SFA for PUFA yields the greatest effect. Fiber is probably a close second to that. We have meta-analysis controlling for confounders, with dose response curves showing that for each gram of PUFA over SFA you lower risk. And also, it appears there is a threshold of risk where the risk does become statistically significant until you reach about 6-8% of daily total caloric intake coming from saturated fat or SFA. So if you stay below that range or threshold of calories coming from SFA you can eat some SFA. And also the SFA to PUFA ratio matters as well. But overall one doesn’t want to exceed the 6-8% of calories coming from SFA mark. SFA risk follows a sigmoidal curve. We have large data analysis on this stuff already. For example, populations with the PCSK9 knock-out gene which causes them to have very much lower LDL (and AppB since all LDL Carrie’s the ApoB tag) have dramatically lower risk of heart disease. About 80% compare to average population, if I recall correctly. They’re the population that drug companies modeled PCSK9 drugs after. We also know that in populations that have a ApoB of less than 40, they virtually never get atherosclerotic heart disease. Tom Dayspring is a world renowned lipid specialist who talks a lot about this stuff. Pretty amazing stuff!

[victoriajohnson]

Can you speak to A2 dairy with APOE4? Good, bad?

[StephenMarkTurner]

Not that it is a big deal, but you appear to be in mirror image. Thanks for this info. I know you would get 100 times the views if you were downplaying saturated fat and ldl (and perhaps selling berberine), I appreciate the integrity.

[unseenatnoonday]

I have 2 copies of APEO4, which I found out by accident and wish I had not. No one on either side of the family has had Alzheimer's or Parkinson's. No one has had dementia. I try to avoid PUFAs, for multiple reasons. I follow the style of eating popularized by Ray Peat, PhD, who says to avoid PUFAs, including fish oil, which I cannot take anyway because I have a genetic condition that causes easy bruising and bleeding. This eating style also advocates milk, fresh squeezed tropical juices (OJ, mainly), honey, some root veggies, saturated fats, and balance of macros at each meal/snack, favoring simple carbs (not complex ones), moderate protein, and a little saturated fat. This way of eating for 1 year improved all my labs dramatically, including glucose (was higher on keto), cholesterol (down to 166, with normal LDL and low triglycerides), and normal CRP for the first time in my 60 years of life. So, as usual. nutritional advice is in the Dark Ages still, and I've had to experiment on myself. My exercise is limited to 30 minutes a day because of my chronic pain condition (EDS), so it still seems that there is little to nothing I can do to prevent Alzheimer's disease, which my migraine neurologist says I shouldn't worry about anyway because family history trumps copies of APOE4. One interesting point that my neuro brought up that I never see mentioned elsewhere is that no one has recruited for a study all those with 2 APEO4 alleles who do NOT exhibit Alzheimer's. Meanwhile, most people with the allele who are included in studies self-select into them because these people are already having symptoms and/or family history. At any rate, PUFAs such as seeds and nuts drive up inflammation; good saturated fats like milk do not--at least not in my body and not in Ray Peat's body of work. Restricting PUFAs also lowered the intensity and frequency of pain.

[sadiqshah]

I read this somewhere in clinical trials which read “Problem is EPA conversation to DHA in nuts and seeds is very poor hence the fish or fish oil or supps “

[markmacdonald]

You said that APOE4 carriers should reduce LDL but didn't really say why. Cold you please clarify and state the main studies etc

[angela]

This is great information for those who are familiar with these medical terminology, scientific names and reading, not to those who are ordinary people like those of us who are following you two for simplification down to earth vocabularies. If my knowledge was at your level, I would have not listen to you or follow you. Please make these information to the level of your audience? Greatly appreciate your time and knowledge!!!