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Introduction

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

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 or Ancestry 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 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

Graphic source: "Advances in the prevention of Alzheimer's Disease" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447057/

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..."

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.

Insulin Resistance

Insulin Resistance is the root of many health concerns, particularly those to which ApoE4s are susceptible. 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


Sleep

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

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 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. 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

Omega-3 (ω-3) fatty acids

Research has shown that Omega-3s (also written as ω-3), and especially DHA, are critical contributors to cell structure and function in the nervous system, and deficits in DHA are associated with cognitive decline during aging and in neurodegenerative disease. While a review of observational and clinical trials that assessed supplementation with Omega-3 fatty acids such as docosahexaenoic acid (DHA) showed that it was not beneficial in symptomatic AD, several did show benefit in the pre-dementia stage of AD, suggesting supplementation may slow early memory decline in E4 carriers.

Main article: Omega-3 fatty acids

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


Other related genes

Genetics makes a substantial contribution to the risk and age of onset of AD. If you have your genetic data from 23andme or other testing sites, you can read more at Alzpedia, a part of Alzforum.org.


Alcohol consumption

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

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 Emeritus Faculty at 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.


Other related topics and deep dives

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


Blood Sugar

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


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

Thiamine

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


Vagus Nerve

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


Resources -- Getting your genetic data

Resources -- where to buy supplements, olive oil, etc.

Resources -- ApoE4-Aware Healthcare Practitioners

Abbreviations and Acronyms

Can be found here.


Fostering and supporting ApoE4 research

Check out some ideas about about what can be done to focus more research on the APOE-ε4 allele and the protein it produces, ApoE4.

Main article ApoE4 Research

Interesting Alzheimer's research projects

Take a 10-minute online test, and have the chance of possibly contributing to a greater understanding of dementia.

Notes