- 1 Introduction
- 2 If you want to check your E4 status
- 3 Just found out you're an E4 carrier?
- 4 What you need to know about E4 and...
- 4.1 Risk of developing the disease
- 4.2 Insulin Resistance
- 4.3 Sleep
- 4.4 Exercise
- 4.5 Ketosis and Ketogenic diet
- 4.6 Fats, Omega-3 &-6, DHA and more
- 4.7 Cholesterol, Lipids and Treatments, including statins
- 4.8 Hormone Replacement Therapy
- 4.9 MTHFR gene, methylation and homocysteine
- 4.10 Other related genes
- 4.11 Alcohol consumption
- 5 Recommended lab tests and all about biomarkers
- 6 The Bredesen Protocol (ReCODE)™ explained for laymen
- 7 Dr Steven Gundry
- 8 Other related topics and deep dives
- 9 Resources
- 10 About This Wiki
The ε4 allele of the APOE gene confers a higher risk for Alzheimer's disease, but numerous other diseases have been linked to E4, including other forms of dementia, heart disease, and gallbladder stones.
These pages have been created in order to organize information about how to prevent and address health issues related to the APOE-ε4 allele. We try our best to aim these at the non-scientist, but the nature of this disease requires some scientific references and terminology to back up these approaches. We've created a list of abbreviations and acronyms to help you in your reading. For simplicity, we often refer to the APOE-ε4 allele as ApoE4 or E4 and Alzheimer's Disease as AD.
If you want to check your E4 status
Before you test, we encourage you to read our post Thinking About Testing? Always good to go in with an informed view of what the results might mean for you.
Some labs will run tests to return your APOE status. Search the Web to find the most recent options for testing.
You can also look at the raw genetic data from a company such as 23andme and look up your results for rs429358 and rs7412. These are referred to as SNPs, which represent variations in your DNA. Once you look up your values for these SNPs, go to this page at snpedia to help you interpret what your results mean.
Just found out you're an E4 carrier?
- If you are new here, we encourage you to read our Welcome Page. Many of our members are E4 carriers and grappled with many of the same questions you might have today.
- For the quickest set of preventive strategies, we put together this summary list, and the steps are related to improving brain health as well as overall health.
- For a great overview about E4, please check out our primer on our forums. It is authored by a member physician who carries two copies of the APOE-ε4 allele, and it offers accessible science background and prioritized, sensible preventative measures.
Note: We know it can be devastating to find out your E4 status, given the inevitable decline with advanced Alzheimer's and the current lack of effective pharmaceutical treatments for it. But we have created ApoE4.Info to help search, organize, and share what we do know about prevention and addressing the early symptoms of AD. As you read through these pages and the forum, you will come to see that there is so much you can do for yourself and your loved ones.
What you need to know about E4 and...
Risk of developing the disease
Many new members want a sense of their lifetime risk. This study (Emmanuelle Genin, et al.) looked at 7,351 cases and 10,132 controls and reported:
"At the age of 85 the LTR [long term risk] of AD without reference to APOE genotype was 11% in males and 14% in females. At the same age, this risk ranged from 51% for APOE44 male carriers to 60% for APOE44 female carriers, and from 23% for APOE34 male carriers to 30% for APOE34 female carriers..." So, part of your risk is also based on gender - women are more at risk than men.
Although being an E4 carrier increases the risk, the number one risk factor for AD is not E4, but aging! Research shows that Alzheimer’s takes a long time to develop and is influenced by numerous factors that can increase risk or provide protection, of which ApoE4 is only one. There are many modifiable risks that you can control.
Decreasing the Population Risk of Dementia
A 24 expert paper in the medical journal Lancet looked at the global burden of dementia and made recommendations about strategies to reduce number of individuals affected. Nonmodifiable risk factors account for 65% of dementia, including a 7% contribution for ApoE𝟄4. Modifiable factors include:
Early Life (<18)
Low Education RR 1.59 PAF 8%
Middle Life (18-65)
Hypertension RR 1.6 PAF 2% Hearing Loss RR 1.9 PAF 9% Obesity RR 1.6 PAF 1%
Later Life (>65)
Smoking RR 1.6 PAF 5% Depression RR 1.9 PAF 4% Physical activity RR 1.4 PAF 3% Social Isolation RR 1.6 PAF 2% Diabetes RR 1.5 PAF 1%
RR is relative risk, PAF is population attributable fraction
Although low educational achievement doesn’t have a particularly high relative risk it is very common globally and thus has a higher impact on the population. Although hearing loss wasn’t considered a risk factor it is associated with dementia and is quite common. Some of the factors that those of us in the west may concentrate on may contribute less to the population burden of dementia.
Livingston et al Lancet 2017; 390: 2673-734 (Available free online with registration)
A graphic can be seen at http://www.thelancet.com/infographics/dementia2017.
Insulin Resistance is the root of many health concerns, particularly those to which ApoE4s are susceptible. Studies have shown that everybody who has Alzheimer’s Disease has insulin resistance in the brain whether or not insulin resistance exists elsewhere in the body. There are many factors which can play in to insulin resistance, but a person is particularly vulnerable to developing insulin resistance if they are sedentary and eat a poor diet, although even individuals of normal weight/BMI can be insulin resistant. A person can be insulin resistant without being Type 2 Diabetic, but Type 2 Diabetes by definition includes insulin resistance.
Main Article: Insulin Resistance
Getting a good night's rest is a critical component of brain health. Good sleep helps remove amyloid beta (Aβ) and reduces oxidative stress. Sleep deprivation increase plaque formation and Aβ aggregation. There is some limited evidence that supplemental melatonin is effective in slowing the progression of MCI and Alzheimer's.
Main article: Sleep
Exercise is good for the brain as well as the body. Exercise in some form or another is probably more critical for ApoE4s than other genotypes.
Main article: Exercise - Types, Lengths, and Benefits
Ketosis and Ketogenic diet
The brain typically gets its energy from glucose (blood sugar), but ketone bodies (ketones) are the brain's main reserve fuel when glucose supply is compromised. Since the uptake of glucose is compromised in Alzheimer’s, a number of ApoE4s have adopted strategies to encourage “metabolic flexibility” which allows the body to easily switch between glucose to ketones to fuel the brain in order to regain or maintain cognitive ability. Ketosis is one of the strategies recommended by Dr Bredesen who has reversed cognitive decline. See also Bredesen Protocol.
Main article: Ketosis and Ketogenic Diet
Fats, Omega-3 &-6, DHA and more
A common diet recommended for ApoE ε4s is the Mediterranean diet because it is high in monounsaturated fats. Another commonly recommended diet is a high fat diet Ketosis_and_Ketogenic_Diet. We know to stay away from unhealthy fats, and saturated fats are said to be ill-advised for ApoE ε4s, but which fats truly are unhealthy?
Additionally, there’s the Omega-3 (also written as ω-3) and Omega-6 (also written as ω-6) factor. Research has shown that polyunsaturated fats high in Omega-3s especially DHA, are critical contributors to cell structure and function in the nervous system suggesting supplementation may slow early memory decline in ε4 carriers. Then there are Omega-6s which are inflammatory, something ApoE ε4s already have a susceptibility towards.
All these factors to consider when trying to follow a healthy diet, and all these terms: Saturated, Polyunsaturated, Omega-3s, Omega-6, DHA,… it can make a head spin. This article attempts to provide understandable background information on dietary fats as well as opportunities and pitfalls that ApoE ε4 should be aware of to maximize healthy fat intake.
Main article: Fats, Omega -3(ω-3) & -6(ω-6), DHA and More
Cholesterol, Lipids and Treatments, including statins
"This is a horrendously complex topic...GLYCAEMIC CONTROL TRUMPS LIPIDS, EVERY TIME. You have been dealt a hand of cards. You need to play them cleverly. IR (Insulin Resistance) is far more damaging than a high LDL, but LDL still matters. We are on a seesaw trying to balance these two. The balance point will be different in everyone." - Stavia, as posted in the Primer. E4s are at higher risk of cardiovascular disease, yet cholesterol is an important component in brain health. How do we resolve the two?
Main Article: Cholesterol, Lipids and Treatments, including statins
Hormone Replacement Therapy
Information coming soon...
MTHFR gene, methylation and homocysteine
There may be an increased risk of carrying both ApoE4 and MTHFR variants. This provides an overview of methylation, methylation genes such as MTHR, and hacking methylation problems including high homocysteine.
Main article: Methylation
Correlative studies have shown that regular consumption of a small amount of alcohol is linked to a number of health benefits, especially cardiovascular benefits, which are correlated with reduced risk of dementia. But the studies are not all consistent, and many researchers speculate that there are too many confounding factors to be able to adequately isolate the effect of alcohol consumption.
More importantly, when the results are stratified by APOE variant, most studies show that even small amounts of alcohol cause harm to ε4-carriers.
Main article: Alcohol consumption
Recommended lab tests and all about biomarkers
From our threads and the research, we've distilled out some important lab testing to start with in order to understand your overall health and give a sense of where to start treatment. We've also included descriptions of various biomarkers and their relevance to ApoE4 carriers.
Common lab tests list is coming...
Main article: Biomarkers
The Bredesen Protocol (ReCODE)™ explained for laymen
Dr. Dale Bredesen Dr. Bredesen has created a protocol that involves multiple interventions to address specific components of AD pathology that research has identified to date. Each intervention is measured and tweaked over time by using blood tests, cognitive evaluations, and other markers of overall health improvements. His analogy is to think of AD as a leaky roof - there are as many as 36 leaks in in the AD roof that need to be addressed to stop the problem. Not every patient will have the same leaks, and the protocol is customized based on the patient’s genetics, current health, and lifestyle.
Main article: Bredesen Protocol.
Here is a summary of Bredesen's book, The End of Alzheimers': http://soler7.com/IFAQ/TheEndOfAlzheimers.html
Dr Steven Gundry
Dr Steven Gundry Wikipedia Gundry has been referenced often within the ApoE4.info forums. He is not an “Alzheimer’s doctor”; he is a cardiothoracic surgeon who, in 2002, changed the direction of his career from surgically repairing the damage of disease to a functional medicine approach of helping patients repair their own bodies with food and supplementation. Shortly after this career change, Dr Gundry began testing for ApoE4 status among the many blood tests on his patients. He has followed thousands of patients with one or two ApoE4 alleles, testing blood markers every three months and advising diet/supplementation accordingly to maintain healthy cholesterol levels, inflammatory markers, cognitive ability, etc. For his specific recommendations for ApoE4s see Dr Steven Gundry’s protocol.
Main article: Dr Gundry's Protocol.
BDNF Brain Derived Neurotrophic Factor
Brain Derived Neurotrophic Factor is produced by neurons and regulates synaptic transmission in the hippocampus. It promotes neurogenesis and nerve growth. Because it plays a critical role in neuronal survival, synaptic plasticity, and memory, BDNF reduction may contribute to synaptic and cellular loss and memory deficits characteristic of Alzheimer’s Disease. BDNF might also explain some of the increased risk of AD in women.
Main article: BDNF
There is substantial evidence that controlling blood sugar levels can have a great impact on the risk of developing dementia.
Main article: Blood Sugar
Coffee (and caffeine)
Much evidence exists that coffee consumption, and caffeine in general (tea will be considered separately), seems to offer some protection against many forms of dementia, including Alzheimer's, regardless of ApoE status.
Main article: Coffee (and caffeine)
Coconuts and coconut products
Coconut oil, and, to a lesser extent, coconuts themselves, have become somewhat popular as a dementia treatment, or preventive measure. The evidence is mixed, but some claim more research will bear out most of the numerous positive claims about it.
Main article: Coconut
Inflammation and LPS (lipopolysaccharides)
Inflammation plays an important role in the pathology of AD. Inflammation can be beneficial, but when left unchecked, inflammation becomes detrimental. “Lipopolysaccharides (LPS), also known as lipoglycans, are large molecules consisting of a lipid and a polysaccharide joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria, act as endotoxins and elicit strong immune responses in animals” (Wikipedia). The Wikipedia page also reports that humans are much more sensitive to LPS than other animals. Lipopolysaccharides are known to induce inflammatory responses and are often used to induce central nervous system inflammation in mouse studies.
Main article: Inflammation & LPS
Thiamine, sometimes spelled thiamin, is also known as vitamin B1. Preliminary evidence suggests that it could help improve the brain's mitochondrial activity by helping optimize its glucose metabolism. Glucose metabolism is compromised in ApoE4 individuals.
Main article: Thiamine
Turmeric and curcumin
There is evidence that turmeric, and in particular one of its components, curcumin, might protect against Alzheimer's and other forms of dementia.
Main article: Turmeric and curcumin
The vagus nerve is a primary carrier of information describing the state of the body to the brain, and also transmits information from the brain back to the body. In 2000, neurosurgeon Kevin Tracey published the results of an experiment where anti-inflammatory drugs in the brain blocked inflammation in the spleen and other organs. He concluded that the brain used the vagus nerve to return the immune system to a place of homeostasis. Researchers are looking to see how the vagus nerve might be used to treat a variety of diseases including cardiovascular disease, autoimmune disease, and Alzheimer's, along with how stimulating the nerve might lead to better health.
Main article: Vagus Nerve
What can I eat? Recipes from our members
Includes the recommendations of ReCode, other noted doctors/research and lab companies.
About This Wiki
These wiki pages are a compilation of information posted to forum threads and research done by individual members. It has not been reviewed by any scientific committee, and represents the nature of the ongoing forum discussions.
And given the pace and disagreements in research, you might find information that is outdated, incorrect, or not relevant. Because we are all volunteers here, the Board has opted for a wiki format, and as new information or even disagreements pop up, it encourages people to edit the wiki directly.
If you'd like to edit the wiki to add to a topic, feel free to jump in. If you do edit, just know that your first edit will be moderated and then you'll be given permission to do further edits without moderation.
Please consider sharing what you know, because we're all experts in something, and your knowledge might just help a fellow E4 traveler.