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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-2015, the wiki is still under construction (indeed, wikis are always under construction -- that's the point!), but much more information will be added in the coming weeks and months -- especially if you, the reader, contribute! Visit the wiki development forum at apoe4.info 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?" Take a look here. "Oh, and what are all these abbreviations I see in the forums?" We've started a list of definitions here.

Introduction

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 [1], protection against severe liver disease caused by hepatitis C [2], and, possibly, slightly greater intelligence in youth [3].

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 There are many researchers sitting on unpublished data looking at lifestyle and even drug interventions and their relation to outcomes based on ε4 status.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:

• Wisconsin Registry for Alzheimer's Prevention (WRAP)

• Cure Alzheimer's Fund

• Alzheimer's Drug Discovery Foundation

Among ADDF's many research efforts is a focus on ApoE. See "Apolipoprotein e4: not just a genetic risk factor"

• 23andMe.

Status: 23andMe is not currently pursuing ApoE-related research.

• Linda Avey's Alzheimer's Foundation (still a work in progress).

• Genomera, a platform for crowd-sourcing research (still in beta).

• Alzheimer's Prevention Initiative

ε4 carriers who feel comfortable sharing their data (anonymously) can upload their sequencing and health information to existing open genome projects:

• Personal Genome Project at Harvard.

• OpenSNP.

Interesting Alzheimer's research projects

• MindCrowd.

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

Note: No cure for Alzheimer’s disease or dementia, nor any scientifically or theoretically well-grounded prevention regimen, is currently known. 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.

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)

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). The evidence is mixed, and the effects on ApoE-ε4 carriers appear to be especially weak, or non-existent.

Main article: Omega-3 fatty acids

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

Melatonin

There is some limited evidence that supplemental melatonin is effective in slowing the progression of MCI and Alzheimer's.

Main article: Melatonin

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

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

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

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

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"

Genetics Alzpedia

Genetics makes a substantial contribution to the risk and age of onset of AD.

Biomarkers

Descriptions of various biomarkers and their relevance to ApoE4 carriers. Includes ApoE4 community test results.

Main article: Biomarkers

Notes

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!