“如果你专注于你无法控制的事情，你的内心就会有点疯狂、愤怒和沮丧。如果你大部分时间都集中在你没有的东西而不是你拥有的东西上，你会非常不快乐。– 托尼·罗宾斯（#1 纽约时报畅销书作家，全国 #1 生活和商业战略家）
嗨，朋友们，我是 Dennis 博士。 感谢您阅读这个关于痴呆症的四篇系列文章（阿尔茨海默病是导致痴呆症的最常见的脑退行性疾病）。 我感谢那些一直在做功课的人，我能鼓励那些第一次加入我的人阅读第一篇博客吗？
朋友们，我们终于见到了房间里的大象——与阿尔茨海默病有关的基因 （APO Epsilon （ε） 4）。 我把这个问题留给这个系列，因为我们无法改变基因组成，知道我们继承了“罪魁祸首基因”可能会产生严重的后果。 但是，我希望将您的注意力转移到可以做的事情上，并帮助您拥抱自己和潜力。 我不相信不尝试就放弃！
基因 – Apo Epsilon （ε） 4 [ ApoE4]
首先，拥有特定的基因 不是 确定性的！ 它将您置于更高的风险类别中，但它并不能确定您是否会表现出这种疾病，在本例中为阿尔茨海默氏症。 换句话说，在“遗传倾向”显现之前，许多因素都在起作用。 在现实生活中，许多拥有该基因的人从未继续发展为阿尔茨海默病，而许多没有该基因的人则患上了阿尔茨海默病。 拥有该基因的一个拷贝 （ApoE4） 确实会使患阿尔茨海默病的风险增加 2 到 3 倍，而拥有两个拷贝会使患阿尔茨海默病的风险增加 8 到 12 倍（图 A）。 让我正确地看待事情：世界上大约 25% 的人口携带一份副本，但只有 2% 的人携带两份副本。 在 APOE 基因家族中，存在等位基因（变异）。 ApoE2,3 和 4。 众所周知，ApoE3 是中性的，E2 提供保护，而 E4 是家族的黑暗之马。 人们认为 ApoE 家族的任务只是在血液中携带脂质，但事实证明 ApoE4 是一种转录因子（一组读取和解释遗传信息的蛋白质）。 这意味着，尽管 ApoE4 与阿尔茨海默病有关，但疾病的表现将取决于 ApoE4 如何读取其他基因。
那么，ApoE4 会发生什么？
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