- 1 About this wiki
- 2 Just found out you're an APOE-ε4 carrier?
- 3 Introduction
- 4 Fostering and supporting ApoE4 research
- 5 Interesting Alzheimer's research projects
- 6 Possible modulators of ApoE4-associated pathology
- 6.1 Alcohol consumption
- 6.2 BDNF Brain Derived Neurotrophic Factor
- 6.3 Blood Sugar
- 6.4 Coffee (and caffeine)
- 6.5 Coconuts and coconut products
- 6.6 Exercise
- 6.7 Genetics Alzpedia
- 6.8 Inflammation and LPS (lipopolysaccharides)
- 6.9 Insulin Resistance
- 6.10 Ketosis
- 6.11 Melatonin
- 6.12 Methylation
- 6.13 Omega-3 (n-3) fatty acids
- 6.14 Thiamine
- 6.15 Turmeric and curcumin
- 6.16 Vagus Nerve
- 7 Biomarkers
- 8 The Bredesen Protocol™ explained for laymen
- 9 Dr Steven Gundry
- 10 Resources -- Getting your genetic data
- 11 Resources -- Events
- 12 Resources -- learning more about APOE
- 13 Resources -- where to buy supplements, olive oil, etc.
- 14 Resources -- APOE-aware healthcare practitioners
- 15 Abbreviations and Acronyms Abbreviations and Acronyms
- 16 Notes
About this wiki
This wiki was created in order to organize information about how to prevent and treat ApoE4-associated pathology. (See Notes, below, for rationale.) As of mid-2016, the wiki is still under construction (indeed, wikis are always under construction -- that's the point of a wiki!), but much more information will be added in the coming weeks and months -- especially if you, the reader, contribute! Visit the at if you have questions about how to contribute or ideas about how these pages should be organized. (Or click on the "Discussion" tab above for thoughts specific to this introductory page.)
Just found out you're an APOE-ε4 carrier?
"I'm feeling overwhelmed! Can I have some basic information about how to stay healthy?" Yes, take a look here.
"Oh, and what are all these abbreviations I see in the forums?" We've started a list of definitions here.
The ε4 variant of the APOE gene is famous for conferring a significantly higher risk for Alzheimer's disease, but numerous other diseases have been linked to it, including, to name a few, other forms of dementia, heart disease, and gallbladder stones. Much of the focus of this wiki space will nonetheless likely be on Alzheimer's disease and other forms of dementia, since dementia is what most ε4 carriers are concerned about, given its devastating consequences and the current lack of effective treatment for it.
While the focus of the wiki will be on illness and its prevention and treatment, it should be noted that possessing an APOE-ε4 allele is not an entirely bad thing for health. A few minor health advantages seem to be conferred by ApoE4, among them, greater absorption or production via sunlight of vitamin D, resistance to malnutrition in children with conditions causing frequent diarrhea , protection against severe liver disease caused by hepatitis C , and, possibly, slightly greater intelligence in youth .
Fostering and supporting ApoE4 research
Here are some ideas about what can be done to focus more research on the APOE-ε4 allele and the protein it produces, ApoE4.
- Encourage researchers to pool existing data to get statistical significance. There are many researchers sitting on unpublished data looking at lifestyle and even drug interventions and their relation to outcomes based on ε4 status. The numbers of ε4 homozygotes in any particular study are in nearly all cases (I'd guess) too small to reach statistical significance, but if the data were pooled it would surely permit some at least tentative, if not solid conclusions. Asking researchers about unreported data on an effect caused by APOE isoform is also a way to raise awareness among them, or to remind them, about how important it is. See "Recent studies that did not report on APOE status."
- Those ε4 homozygotes who are interested in participating in trials could contact researchers and say they are available to be studied (heterozygotes could of course also be studied). Some researchers would jump at the chance to research non-demented ε4 homozygotes, since the expense of finding ε4 homozygotes in younger populations is enormous.
Some research teams or organizations that could be contacted:
Among ADDF's many research efforts is a focus on ApoE. See "Apolipoprotein e4: not just a genetic risk factor"
Status: 23andMe is not currently pursuing ApoE-related research.
ε4 carriers who feel comfortable sharing their data (anonymously) can upload their sequencing and health information to existing open genome projects:
Interesting Alzheimer's research projects
Take a 10-minute online test, and have the chance of possibly contributing to a greater understanding of dementia.
Possible modulators of ApoE4-associated pathology
Alzheimer’s takes a long time to develop and is influenced by numerous factors both risk and protective, of which ApoE4 is only one factor.
The following is a list of putative treatment and prevention measures, or factors that affect risk of dementia or other pathology caused by ApoE4, along with a rationale (be it research support or speculation based on a plausible mechanism of action), with links to research papers.
These modulators are listed in alphabetical, not priority order. If looking for that one strategy that will likely produce the best benefit, read about insulin resistance.
Note: There is no cure for Alzheimer’s disease or dementia, nor any scientifically or theoretically well-grounded prevention regimen, is currently known.
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, themselves, 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
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 development 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
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
Genetics makes a substantial contribution to the risk and age of onset of AD.
Inflammation and LPS (lipopolysaccharides)
Inflammation plays an important role in the pathology of AD. Inflammation can be beneficial, but when left unchecked, 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 CNS inflammation in mouse studies.
Main article: Inflammation & LPS
Insulin Resistance is the root of many health concerns, particularly those that ApoE4s are susceptible to. Studies have shown that basically 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
The brain typically gets it's 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. Ketogenesis is one of the strategies recommended by Dr Bredesen who has reversed cognitive decline. See Bredesen Protocol
Main article: Ketosis
There is some limited evidence that supplemental melatonin is effective in slowing the progression of MCI and Alzheimer's.
Main article: Melatonin
An overview of methylation, methylation genes and hacking methylation problems.
Main article: Methylation
Omega-3 (n-3) fatty acids
Several lines of reasoning have led to the hypothesis that consumption of some, or any omega-3 fatty acids (DHA and EPA, found primarily in fish, and ALA, found in plants) will reduce the risk of dementia and can even improve cognition in youth and in those with cognitive decline. The evidence, however, has been mixed. Until recently, the effects on ApoE-ε4 carriers has appeared to be weak to non-existent.Main article: Omega-3 fatty acids
Thiamine, sometimes spelled thiamin, is the same 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"
Descriptions of various biomarkers and their relevance to ApoE4 carriers. Includes ApoE4 community test results.
Main article: Biomarkers
The Bredesen Protocol™ explained for laymen
Dr. Dale Bredesen of the Buck Institute for Research on Aging is a scientist who has been studying Alzheimer's disease for 25 years and has come up with a way to reverse it in it's early stages. His initial protocol involved 25 different interventions which individually don't make a big difference, but together are quite powerful. Each intervention is tweaked over time by using blood tests, etc. to measure their effect. In his initial paper, nine out of ten patients reversed their memory problems. The one who didn't show improvement was past the early stages of Alzheimer's.
Dr. Bredesen has since expanded the protocol and number of patients seen and is in the process of opening up trials to the wider public through MPI Cognition. He was previously affiliated with Muses Labs. This page sets out to explain the strategies utilized in simple enough language that untrained people suffering from Alzheimer's (or their caregivers) can begin to implement the easier ones, and work with their doctors or other labs to begin the others.
Main article: Bredesen Protocol.
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’s 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.
Resources -- Getting your genetic data
Resources -- Events
Resources -- learning more about APOE
Resources -- where to buy supplements, olive oil, etc.
Resources -- APOE-aware healthcare practitioners
Abbreviations and Acronyms Abbreviations and Acronyms
In response to https://www.23andme.com/you/community/thread/15952/. (You need an account at 23andMe to follow this link. Demo accounts, which are free, work fine.)
Thanks to SNPedia for hosting an earlier version of this wiki!