Hi friends, Dr Dennis here. Thanks for reading this series of four on all things Dementia (Alzheimer’s is the most common brain degenerative disease that leads to Dementia). I am thankful for those who have been doing their homework, and may I encourage those who joined me for the first time to read from the first blog?
Friends, we have finally met the elephant in the room—the genes (APO Epsilon (ε) 4) implicated in Alzheimer’s disease. I have left this to this series because we can’t change the genetic makeup, and knowing that we have inherited the “culprit genes” could have grave consequences. However, I hope to shift your focus to what can be done and help you embrace who you are and your potential. I don’t believe in giving up without trying!
The Gene – Apo Epsilon (ε) 4 [ ApoE4]
First, having a particular gene is NOT deterministic! It puts you in a higher risk category, but it doesn’t determine if you are ever going to manifest the disease, in this case, Alzheimer’s. In other words, many factors are at play before a “genetic tendency” manifests itself. In real life, many with the gene never go on to develop Alzheimer’s, and many without the gene do. Having one copy of the gene (ApoE4) indeed increases the risk of developing Alzheimer’s by two to three-fold, and having two copies increases the risk by eight to twelve-fold (pic A). Let me put things in perspective: about 25% of the world’s population carries a single copy, but only 2 % carries two copies. In the APOE gene family, there are alleles(variation). ApoE2,3 and 4. It is well established that ApoE3 is neutral, E2 confers protection, and E4 is the dark sheep of the family. It was thought that the ApoE family was only tasked to carry lipids in the blood, but it turns out that ApoE4 is a transcriptional factor (a group of proteins that read and interpret genetic information). This implies that although ApoE4 is implicated in Alzheimer’s disease, the manifestation of the disease will depend on how ApoE4 reads the other genes.
So, what happens with ApoE4?
ApoE4 is thought to mediate the disease manifestation through the following mechanisms:
- Pro-Inflammatory – ApoE4 increases inflammatory response, the innate system (one of the two central systems of our defence). Inflammation is essential to fighting “unwelcoming intruders” (1). However, if prolonged and unchecked, it will become chronic inflammation, especially if the underlying causes are not recognised. Therefore, we must identify the root causes rather than forcibly trying to dampen the inflammation. I will explore ways to reduce and identify the causes later in other series, so keep checking my blogs.
- ApoE4 can cause misfolding of Amyloid protein (the AHA molecule, series 1, week 4) and Tau and reduce its clearance. As I have pointed out above, inflammation is essential in fitting intruders, but too much will lead to disaster, especially in the presence of genetic tendencies. Increased Amyloid protein deposition will lead to rapid accumulation of Tau inside the cells, and we will have a “double whammy” situation. Therefore, identifying inflammation triggers can prevent excessive Amyloid deposition even if we have the genes.
- ApoE4 carriers have brain scan evidence of reduced glucose metabolism as early as their 20’s! (2) and this is thought to be due to insulin resistance. Glucose is a natural ingredient used by all body cells to survive. The glucose uptake relies on insulin, and we cannot use glucose in the presence of insulin resistance. This is thought to be the cause of Alzheimer’s (the gradual brain glucose exhaustion). Sounds painful! However, thank goodness the researchers, including Dr Dale Bredesen MD, showed we can train our brain cells to use alternative fuel, ketones (3).
- Outside our brain, ApoE4 carries an increased risk for Cardiovascular (CVD) disease. It is also thought to be due to the pro-inflammatory tendencies.
Friends, enough for today? It is tough to stomach these facts, but it is not hopeless. We have evidence of ways to prevent and even reverse these risks. Stay tuned! More to come. I have deliberately released information slowly as too much, too quickly will cause indigestion 😊
What are the main take-home messages?
- About 25% of the world’s population carries one copy of the ApoE4 allele. Having single and two copies of ApoE4 increases the risk of Alzheimer’s overall by about 15% lifetime risk.
- ApoE4 is an inflammation-induced gene; it enhances the inflammatory response to fight infection but, if left unchecked, predisposes the brain to Amyloid (the AHA molecule) insults and cell death.
- We don’t have to look far for solutions, and we don’t complicate management. It will all be revealed slowly to those committed to staying the course.
Friends, in part 2 of this blog, we will continue to explore other possible interactions between ApoE4 genes and other cellular functions. See you real soon in the coming Biology lesson!
Please call my PA, Melissa, on 0422 678 660, leave a message, or email info@mind4lifecoaching.com.au, and we will respond to you if you have any questions.
The Potential Solutions
- Use anti-inflammatory recipes, such as ginger, curcumin, Omega-3, etc.
- Ketoflex 3/12 diet – Induce ketosis. Ketones provide alternative fuel for neurons in the absence of glucose or in the presence of insulin resistance, which disabled the neurons from utilising glucose as an energy source. More on this later!
- MCT oil (Medium chain Triglyceride) as part of a ketogenic diet. Source of MCT oil – Palm kernel and Coconut oil.
- Other supplements – Resveratrol, Vit D3, Magnesium, Ubiquinol (Co-enzyme Q10), Herbs (Ashwagandha, Turmeric, Hericium Erinaceus/Lion’s mane).
- Exercise – 30 mins per day.
- Stress management – mindfulness and relaxation.
- Brain training – cognitive stimulation games. More on this later!
Friends, there is a lot more information about these on the internet. Please feel free to do your research.
Please call my PA, Melissa, on 0422 678 660, leave a message, or email info@mind4lifecoaching.com.au, and we will respond to you if you have any questions.
References
- Role of apolipoprotein E4 in protecting children against early childhood diarrhea outcomes and implications for later development – PMC
- APOE and Alzheimer’s Disease: Neuroimaging of Metabolic and Cerebrovascular Dysfunction – PMC
- Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer’s Disease – PMC