Main Page

From ApoE4.Info Wiki
Revision as of 09:26, 13 March 2021 by Nf52 (talk | contribs) (Changed title on ApoE 4 research)
Jump to navigation Jump to search

Introduction

APOE, short for Apolipoprotein E, is both a protein and a gene. As a protein ApoE is involved in the metabolism of fats (lipids) in the body and comes in different isoforms: ApoE2, ApoE3, ApoE4. As a gene it is polymorphic, that is to say a gene with multiple variations called alleles. They go hand in hand, the ApoE gene tells the body how to make the ApoE protein. To distinguish the allele from the protein the lower case Greek letter epsilon “ε" is sometimes added. The three ApoE alleles are: ApoE ε2, ApoE ε3, and ApoE ε4.

Everyone gets one allele from their mother and another from their father. For example, when someone says they are a 3/4, that means one ApoE ε3, and one ApoE ε4. When someone says they're homozygous, they're a 4/4, if heterozygous they're either a 2/4 or a 3/4.

The ApoE ε4 allele is the oldest of the ApoE variants, having existed literally since the dawn of man. For 96% of human history, we were all ApoE4 homozygotes (ε4/4s). The other alleles showed up “recently” in evolutionary terms. ApoE3 appeared 220,000 years ago, it now dominates in numbers, and 80,000 years ago ApoE2 appeared.

Frequency of ε4 is low (light red regions) and high (dark red regions). The gray color indicates that there are no data available for this country. Source: https://www.frontiersin.org/articles/10.3389/fnins.2021.630502/full

From APOE and Alzheimer’s Disease: From Lipid Transport to Physiopathology and Therapeutics (Mohammed Amir Husain et al, 17 Feb 2021):

The world-wide frequency of human APOE alleles varies considerably. APOE3 is the most common among all human populations and its frequency ranges from 85% (Asia) to 69% (Africa) (Singh et al., 2006). APOE4 allele frequency varies considerably in native populations of Central Africa (40%), Oceania (37%), and Australia (26%) (Corbo and Scacchi, 1999). The distribution across Europe and Asia follows an apparent gradient from north to south, with low APOE4 allele frequencies in the Mediterranean or South China and higher frequencies in northern regions (up to 25%) (Egert et al., 2012). APOE2 is the least common allele with a global prevalence of 7.3% and is absent in many indigenous people without any clear regional pattern (Corbo and Scacchi, 1999; Singh et al., 2006).

It’s theorized that the ε4 allele was quite beneficial in allowing early man to survive through variable food availability and inflammatory conditions like wounds and walking on dung. But in today’s world of plentiful, industrially produced, artificially sweetened, processed food, environmental insults, artificial lighting, high stress, low sleep, sedentary lifestyle, and other factors, the gene doesn’t seem to be responding well. In our modern environment, the ε4 allele of the gene confers a higher risk for Alzheimer's disease and other medical conditions.

APOE genotypes can affect many cellular functions such as synaptic integrity, lipid transport, glucose metabolism, Aβ clearance, BBB integrity or mitochondria regulation. Abbreviations: apoE, apolipoprotein E; NFT, neurofibrillary tangle; BBB, blood brain barrier; IL, interleukin; TNF-α, Tumor necrosis factor-α; ROS, reactive oxygen species. Source: https://www.frontiersin.org/articles/10.3389/fnins.2021.630502/full

These pages have been created in order to organize information about how to prevent and address health problems 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 get tested, 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.

Many labs can test your APOE status. Search the Web to find the most up-to-date 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 convert the results into your APOE status.

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 Alzheimer's 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! According to Genome-Wide Association Study of Brain Connectivity Changes for Alzheimer’s Disease (Samar S. M. Elsheikh, et al Jan 2020) the effects of ApoE4 account for only 27.3% of the overall disease heritability. 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 factor. There are many modifiable risks that you can control.

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

Decreasing the Population Risk of Dementia: A 2014 study by a team of U.K. and USA authors reviewed the “Potential for Primary Prevention of Alzheimer’s Disease.” Seven potentially modifiable risk factors having consistent evidence were: diabetes, midlife hypertension, midlife obesity, physical inactivity (sedentary), smoking, depression and educational attainment (curiously diet is not separately identified). Considering that the risk factors were not independent they accounted for nearly 30% of Alzheimer’s cases with physical inactivity being the largest proportion in the UK, USA, and Europe. “Risk factors associated with the onset and progression of Alzheimer’s disease: A systematic review of the evidence,” by Mona Hersi, et al, was published in the Journal of Neuro Toxicology, https://doi.org/10.1016/j.neuro.2017.03.006). Ninety three primary reviews of studies on risk factors covering four hundred and thirty two studies published between 2010-2012 were evaluated. “Highlights are: Inherited or “familial” cases of Alzheimer's account for less than 5% of all cases, Several factors including age, head injuries, smoking, lower social engagement, sedentary lifestyle, and the APOE e4 gene are associated with increased risk, Several factors including statins, light to moderate alcohol intake, physical and cognitive activities and APOE e2 gene are associated with decreased risk. A number of risk factors are potentially modifiable and may be targeted for prevention.

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.

Other health conditions besides Alzheimer's

The ε4 variant of the ApoE gene is famous for its association with Alzheimer’s Disease but other conditions have also been linked to it: other forms of dementia, other brain disorders, high cholesterol, cardiovascular disease, infectious disease susceptibility, and gallstones.

Main Article: ApoE ε4 and health conditions besides (or maybe contributing to) Alzheimer’s

Of non-white or non-European descent

Minorities are underrepresented in health studies, most research on APOE-ε4 and Alzheimer’s has been conducted on white subjects of European descent. Further compounding this situation is that much of the research conducted on health conditions that affect ApoE4s: Alzheimer’s, Cardiovascular disease, shortened longevity, etc. often do not stratify by APOE status much less racial/ethnic status. One would think genes are color blind, and yet there are differences in non-European ApoE4s. So what to believe? This wiki is dedicated to sharing what research is available.

Main Article: Non-white or non-European descent

Insulin Resistance

If there is just one strategy an ApoEε4 can pursue, it should be reducing Insulin resistance. Insulin Resistance (IR) is the root of many health concerns, particularly those to which ApoEε4s are susceptible. Insulin Resistance is very common, it’s been estimated 50% of the US population has it. IR develops slowly (over decades), silently, and typically goes undiagnosed. Insulin resistance (IR) does not equal Type 2 Diabetes (T2D), although T2D is one of the possible end points of insulin resistance. A person can have what is conventionally thought of as good blood glucose (blood sugar) levels, feel that they’re healthy, but be insulin resistant. Understanding insulin resistance and the strategies to improve insulin sensitivity is vital to ApoEε4 health. 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.

Insulin Resistance in the brain

The brain needs a lot of fuel, more than any other organ in the body, and it needs it 24 hours a day. Insulin is critical to providing the brain with the adequate amount of energy it needs. There is a clear connection between insulin resistance and Alzheimer’s Disease. The term Type 3 Diabetes was coined over 10 years ago to describe Alzheimer’s Disease and the moniker still persists today, having only been reinforced with further research.

Main Articles: Insulin Resistance and

Insulin Resistance in the brain

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


Stress

The four pillars to prevent/reverse cognitive decline are: Diet, Exercise, Sleep and reducing Stress. The body’s response to stress provides protective measures when the stress is short lived, but modern western lifestyle subjects us to multiple and constant stressors. Constant stress over the long term is damaging to the entire body, not just the brain and ApoE4s seem to be even more susceptible to the negative effects of stress.

Main article: Stress


Mitochondria

Mitochondria produce energy for our bodies, particularly the energy hungry brain. Mitochondria also contribute to potentially harmful oxidative stress. When the balance between producing beneficial energy and damaging oxidative stress is disrupted, mitochondria become damaged and can enter a downward spiral of degraded energy production resulting in even greater damaging effects. Mitochondrial dysfunction is a major determinant in how we age, is a key factor in a myriad of diseases, and in particular is one of the earliest and most prominent features of Alzheimer’s Disease.

Main article: Mitochondria


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. But ketosis has medical benefits beyond just providing an source of energy for the brain, it also reduces inflammation. 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. (Read Insulin Resistance for info on glycemic control). 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


Gut-Brain Connection: Leaky Gut/Leaky Brain, Microbiome (gut bugs)

Health of the gut plays an important role in the health of the brain. Inflammatory lifestyle and dietary habits can lead to a disrupted gut microbiome and a “leaky gut.” Leaky gut, in turn, can lead to “leaky brain” which triggers neuroinflammation. Additionally, research shows that there is a difference in microbiota diversity and abundance for ApoE4s.

Main Article: Gut-Brain Connection: Leaky Gut/Leaky Brain, Microbiome (gut bugs)


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 make 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


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 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... in the meantime, there's a summary of key tests for ReCode Protocol Taken from Dr Bredesen's book The End of Alzheimer's in the Bredesen Protocol write-up.

Main article: Biomarkers

The Bredesen Protocol (ReCODE)™ explained for laypeople

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.

Scientific support for a high protein diet

Individual differences aside (though very important), some forum members find the literature and concepts supporting a higher protein, higher leucine diet in the absolute sense to be more persuasive than the epidemiological studies used to underpin low protein recommendations. Caveats can include implementing higher protein in a way that avoids chronic stimulation of mTOR and choosing traditionally raised meat, eggs and dairy. From this perspective, Don Layman and other long-time protein metabolism researchers have 1) presented a cogent case supporting near lifelong higher protein intakes that should be considered when formulating a personal protocol, and 2) established that the need for protein above the RDA will apply one way or another to nearly everyone if not everyone. Animals are preferred for a number of reasons, but plant proteins can be combined to support protein metabolism in vegetarians and vegans.

Main article: Scientific support for a diet higher in protein than the RDA.

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 (also known as blood glucose) levels can have a great impact on the risk of developing dementia.

Main article: Blood Sugar


Cannabinoids, Cannabidiol (CBD), THC, HEMP, Marijuana, Cannabis

Products from cannabis plants (both hemp and marijuana) offer many health benefits of interest to ApoE4 carriers and can enhance a program addressing lifestyle strategies. From decreasing Amyloid-beta plaque, offering neuroprotection, aiding in generating new neurons, lowering inflammation, assisting with insulin sensitivity, helping with stress, improving sleep and helping maintain hormonal balance.

Main article: Cannabinoids, Cannabidiol (CBD), THC, HEMP, Marijuana, Cannabis


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)


Coconut Oil, MCT oil, and other Ketone/Cognition Boosters (salts, esters)

Ketones are a source of fuel for the body, especially the brain. With certain dietary/lifestyle approaches the body can make its own ketones but there are also products that can be consumed for rapid conversion to ketones in the body to aid brain function: coconut oil, MCT oil, salts, esters etc. There are positive and negative aspects to using these products as well as particular considerations for ApoE ε4s.

Main article: Coconut Oil, MCT oil, and other Ketone/Cognition Boosters (salts, esters)


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


Oxalates, a potential problem for Keto, Paleo and vegan diets

Most people have heard of oxalates because of their connection to kidney stones. Or perhaps with regards to spinach, because the calcium in spinach is bound by oxalates, and not considered a good source of calcium. Here's some background on what makes oxalates so toxic to humans and why they might be the missing link to improving your health.

Main article: Oxalates


Resveratrol

Resveratrol treatment has been shown to reduce neuronal inflammation and improve cognitive performance by mitigating reactive oxygen species, inhibiting pro-inflammatory molecules such as cyclooxygenase-1, or COX1, and inhibiting beta-amyloid plaque formation and aggregation.

Main article: Resveratrol


Sirtuins

Sirtuins are crucial cellular proteins that hold sway over a broad range of physiological processes, including circadian regulation, anti-inflammatory activity, metabolic adaptations, and neurological protection. As such, they present a promising therapeutic strategy to ameliorate age-related diseases and extend healthspan. The focus of current sirtuin-related research is centered on the use of NAD+ supplementation or sirtuin-activating compounds such as resveratrol to boost sirtuin activity to revert the disease process and promote healthy aging.

Main article: Sirtuins


Thiamine

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 tumeric 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

Advance Directive for Dementia

Standard advance directives don't adequately address medical scenarios faced by dementia patients; at the same time, these patients may no longer have the executive functioning necessary to think such decisions through when the need occurs. Consequently, countless Alzheimer's and other dementia patients are not necessarily given the care they would desire at different stages of the disease, while caregivers can suffer deep anxiety trying to guess what their loved one with dementia would want. This section provides a free dementia advance directive form you can fill out and add to your other end-of-life papers. It also provides links to online discussions of the issues that people may want to consider.

Main Article: Advance Directive for Dementia

"How-To" Get the most out of the ApoE4.info website

A "How-To" guide for new and not-so-new members. We hope you will browse this user-friendly guide. It includes screenshots and step-by-step directions for such useful actions as posting on the site, using quotes to notify members of a response to their post, using hyperlinks to articles or other forum topics, subscribing to a favorite topic, and using Private Messages. Link to the Guide: "How-To" Get the most out of the ApoE4.info website

What can I eat? Recipes from our members and Recommended food websites/blogs

Abbreviations and acronyms

Searching for a Healthcare Practitioner

A list of ApoE4-Aware Healthcare Practitioners

A List of ApoE4-Aware Health Coaches

Health coaching is a client-centered process in which the client determines their own path and the coach provides the support and encouragement to make positive and lasting lifestyle changes. Coaches guide the client to create a vision for their health and help them set goals to achieve that vision. Coaches can supply information and education, work with clients to explore options, brainstorm, prioritize, set goals, help them stay accountable, explore barriers, and celebrate successes. For improving or preventing cognitive decline, health coaches can support clients as they learn about healthier lifestyle options and work to improve their diet, exercise, sleep, relaxation, social engagement or any other habits to reach their health goals. Note: coaches will most likely will not be physicians, physician assistants, or nurse practitioners, so will not be ordering or interpreting lab tests, or prescribing medicine.

Direct to Consumer Lab Testing Options

ApoE4.Info members often find that their health insurance (including Medicare) does not cover certain tests that they deem not "medically necessary". You can check with your insurance company to determine if they cover the tests you plan to request. For example, a lipid profile or Vitamin D test may be considered medically warranted for certain populations.

If the tests you want aren't covered by insurance, or you don't have a practitioner who will order them, you can use a Direct-to-Consumer Lab Testing company. You decide which tests to order and the results are sent only to you.

Lab result tracking and sharing

The 'ApoE4.Info Biomarker Targets, Ranges and Labs' spreadsheet includes biomarker targets recommended by noted doctors/researchers and lab companies, including Dr. Bredesen's ReCode recommendations. To use it as a base to track your own results, open the sheet and choose File / Make a copy. (If you only see the Download option, click the Sign in button in the upper right corner, and log in using your Google account.)

Please note:

1) While you are signed into Google and using the spreadsheet in the same browser, your Google ID will show to others in the upper right corner of the spreadsheet. Neither ApoE4 nor those who contribute to this spreadsheet will be responsible for your identity becoming known in this way.

2) If you copy or download this spreadsheet for your own use, entries in the master spreadsheet are likely to change over time and will not be reflected in your own version.

You can also add your results to the public Community Test Results spreadsheet if you would like to share them with others.

Getting your genetic data

Where to buy supplements, olive oil, etc.

Clinical Trials and Patient Registries focused on Alzheimer's and Related Dementias (AD/RD)

ApoE4 Research: What's New And What YOU Can Do

Many Alzheimer's related clinical trials are researching lifestyle or non-drug interventions. Most do not require you to change whatever lifestyle strategies and interventions you are currently using to optimize your health. Do Something Great! Watch a whiteboard video from UsAgainstAlzhiemer's to learn more about clinical trials, and why you should “do something great” and sign up for one. Right now, 80% of studies are delayed because too few people sign up to participate. <ref>https://www.endalznow.org/why-join</ref>
Main Article: ApoE ε4 Alzheimer's Research: What's New and How YOU Can Accelerate Research

"Why I Participate":

Here are some short (2-minute) videos from the U.S. National Institute on Aging (part of the U.S. National Institutes of Health) with real people who don't have Alzheimer's explaining why they participate in prevention research, providing information about their experiences and comments from their Study Doctors on the importance of their participation in advancing prevention and treatments.

Why I Participate in Alzheimer's Research - Kay's Story
Why I Participate in Alzheimer's Research - Bob's Story
Why I Participate in Alzheimer's Research - Kerretha's Story
Why I Participate in Alzheimer's Research - Will's Story

Opportunities to Participate in Patient Registries and Observation Studies from 18-80+

All of Us.
  • "All of Us is sponsored by the U.S. National Institute of Health and is "inviting one million people across the U.S. to help build one of the most diverse health databases in history. We welcome participants from all backgrounds. Researchers will use the data to learn how our biology, lifestyle, and environment affect health. This could help them develop better treatments and ways to prevent different diseases. Adults of any age are welcome! [/quote]
Alzheimer’s Prevention Registry.
  • The Alzheimer's Prevention Registryis an international effort to help identify pre-symptomatic treatments or interventions that will postpone, slow, or prevent Alzheimer’s disease progression. This focus on prevention launched a new approach to Alzheimer’s research by evaluating the most promising therapies at the earliest possible stage of the disease process in cognitively normal people who, based on age and genetic background, are at highest risk of developing Alzheimer’s symptoms. The goal of API is to identify pre-symptomatic treatments or interventions that will postpone, slow, or prevent disease progression. [/quote]You can learn more about joining this registry for notification of current and future research trials here and will then also get periodic newsletters about new research findings: [url=https://www.endalznow.org][color=#00BF00][b]End Alzheimer's Now[/b][/color][/url]
APT Web Study

APT Web Study is an innovative project of the Alzheimer's Clinical Trials Consortium (ACTC), a network of dozens of academic research centers collaborating to accelerate research, with funding from the U.S. National Institute on Aging. The APT Web Study is seeking for people who are 50 years or older and interested in accelerating AD research. Using an online, easy to use testing program that you can do on a laptop or tablet, they offer:

  • Access to secure, personalized, web-based tools to assess and track your cognitive performance
  • Opportunity to participate in comprehensive evaluations at one of our nationwide clinical sites
  • Opportunity to participate in clinical trials to prevent Alzheimer’s disease

You can view a brief video explaining the APT Web Study here.

TrialMatch™
  • TrialMatch™ " is a service that provides customized lists of clinical studies based on user-provided information. The free, easy-to-use platform allows you to see which studies are a good fit for you or a family member. Search for studies, sign up for study updates, or connect with researcher teams.
  • As TrialMatch™ says: "Don't just hope for a cure — help us find one."

Clinical Trials Currently Recruiting with a focus on ApoE4

  • Note: We strongly recommend reading some of the sections below to learn more about clinical trials. The decision to contact any clinical trial site to begin the screening and enrollment process is a personal one that only you and a "study partner", if involved, can make. All clinical trial information may be changed by the trial sponsors or outside evaluates and studies may end with little to no advance notice.
  • The links provided below are from the ClinicalTrials.gov website. More tips on searching for clinical trials are listed below and by linking here: NIH ClinicalTrials.gov: Learn About Clinical Trials

Transcranial Photobiomodulation for Alzheimer's Disease (TRAP-AD)March 5, 2021, will recruit amnestic MCI patients for "light therapy" in Boston and NYC

Biomarker Effects of ALZ-801 in APOE4 Carriers With Early Alzheimer's Disease. Last Updated Jan. 5, 2021

Gene Therapy for APOE4 Homozygote of Alzheimer's Disease Last Updated Feb. 2, 2021

Imaging of Brain Structural/Functional Connectivity and Amyloid and Tau Lesions in APOE4 Carriers. (Protocol Z Not Yet Recruiting; Last Updated Oct. 30, 2020

Network-Level Mechanisms for Preclinical Alzheimer's Disease Development Last Updated Oct. 1, 2020

Prevention of Cognitive Decline in ApoE4 Carriers With Subjective Cognitive Decline After EGCG and a Multimodal Intervention ((PENSA) Location: Barcelona, Last Updated March 5, 2020

Hearing Aid and Individuals With Cognitive Disorders Requires hearing loss and AD diagnosis with ApoE4; locations Iowa and TN; last updated Feb. 25, 2020

DHA Brain Delivery Trial (PreventE4) Last Updated 2019; study continues through 2023; Location: USC-Los Angeles, CA)

AHEAD 3-45 Study: A Study to Evaluate Efficacy and Safety of Treatment With Lecanemab (BAN2401) in Participants With Preclinical Alzheimer's Disease and Elevated Amyloid and Also in Participants With Early Preclinical Alzheimer's Disease and Intermediate Amyloid Multiple US locations; also Australia and Canada, Last Updated Dec. 16, 2020

Links to Recent Forum Topics on Alzheimer's-Related Clinical Research

This section aims to provide an easy way to browse some of the latest findings of research posted on the ApoE4.info forums, especially Science and Research and Prevention and Treatment that may be helpful to you and that were only possible through participation of people like ApoE4.info members.

Recent Advances in Lifestyle Prevention of AD/RD from Clinical Trials

  • Richard Isaacson, M.D. is Director of the Alzheimer's Prevention Clinic in NYC. In this 2018 review,Clinical Application of APOE in Alzheimer’s Prevention: A Precision Medicine Approach (2018) he and his team describe clinical trials that resulted in recommendations for targeted lifestyle interventions that are specific to APOE ε4 carriers. These include factors related to lifestyle, nutrigenomics (the effect of food on our genes), pharmacogenomics (the study of how our genes affect our responses to drugs), AD comorbidities (conditions associated with an increased risk of AD), and other biological and behavioral considerations. "Using a clinical precision medicine strategy that incorporates APOE ε4 carrier status may provide a highly targeted and distinct approach to AD prevention with greater potential for success." Here's what people like you who participated in research demonstrated about the benefits of physical activity in preventing Alzheimer's disease in ApoE4 carriers:
Physical activity
  • "A systematic review of 16 prospective studies concluded that physical activity decreased the risk of developing AD by 45%
  • "Physically active ε4 carriers had an OR [odds ratio risk of Alzheimer's] of 2.30 and sedentary ε4 carriers had an OR of 5.53
  • "Aerobic activity was associated with greater cognitive performance for ε4 carriers compared to non-carriers)".
  • "Sedentary individuals who were ε4 carriers had significantly higher levels of brain Aβ and lower levels of CSF Aβ42 compared to sedentary non-carriers, findings associated with AD pathology"
  • Dr. Isaacson notes that results of these studies with ApoE4 participants "have important implications for physical activity recommendations and suggest that increasing physical activity, while important for all AD prevention patients, may have more pronounced effects in ε4 carriers compared to non-carriers. The findings also suggest that physical activity may prevent Aβ accumulation that occurs in the brains of ε4 carriers before clinical symptoms of AD even become apparent

Flu, Pneumonia Vaccinations Tied to Lower Risk of Alzheimer's Dementia (July 2020)
Three research studies suggest that:

  • "At least one flu vaccination was associated with a 17% reduction in Alzheimer’s incidence. More frequent flu vaccination was associated with another 13% reduction in Alzheimer’s incidence."
  • "Vaccination against pneumonia between ages 65 and 75 reduced Alzheimer’s risk by up to 40% depending on individual genes."
  • "Individuals with dementia have a higher risk of dying (6-fold) after infections than those without dementia (3-fold)."
  • "With the COVID-19 pandemic, vaccines are at the forefront of public health discussions. It is important to explore their benefit in not only protecting against viral or bacterial infection but also improving long-term health outcomes,” said Maria C. Carrillo, Ph.D., Alzheimer’s Association chief science officer. “It may turn out to be as simple as if you’re taking care of your health in this way — getting vaccinated — you’re also taking care of yourself in other ways, and these things add up to lower risk of Alzheimer’s and other dementias,” Carrillo said. “This research, while early, calls for further studies in large, diverse clinical trials to inform whether vaccinations as a public health strategy decrease our risk for developing dementia as we age.”[Emphasis added.]

Blood Tests for Tau and Amyloid may replace need for PET scans and spinal taps and improve diagnosis July 2020'

  • A bit of background: Per Dr. Richard Isaacson of Cornell Weill Medicine's Alzeheimer's Prevention Program, "APOE ε4 carriers are at increased risk for developing AD and increased risk for developing the disease at an earlier age... Furthermore, studies have shown that individuals with two copies of the ε4 allele are at even greater risk, and the odds ratios for developing AD based on APOE is 5 times greater in APOE ε4 homozygotes [ApoE 4/4] compared to heterozygotes [ApoE 3/4 or 2/4]. Imaging studies have further supported these findings by demonstrating that APOE ε4 carriers have higher levels of brain amyloid-β (Aβ) and lower levels of CSF Aβ42 compared to non-carriers, findings that are associated with AD pathology. Clinical Application of APOE in Alzheimer’s Prevention: A Precision Medicine Approach (2018)===
  • A blood test for Alzheimer’s disease that incorporates both amyloid and tau measures may allow earlier and more accurate dementia diagnoses not only in research participants but also in patients referred to Memory Clinics for evaluation of possible cognitive impairment.
  • PET scans and spinal taps in healthy participants in clinical trials shows that not everyone with amyloid and tau develops AD/RD, BUT people with amyloid and tau are more likely to be diagnosed within 10-20 years with AD/RD.
  • As many as 30% of people in early studies of Alzheimer's may have had an incorrect diagnosis! Accurate blood tests to screen and monitor those at risk of AD/RD are crucial to finding ways to prevent, delay or treat these slow-moving diseases.
  • Scientists from St. Louis, Missouri launched the SEABIRD Study (Study to Evaluate Amyloid in Blood and Imaging Related to Dementia) (SEABIRD) "to develop and validate Alzheimer’s blood biomarkers in a cohort that is more diverse and representative of the greater St. Louis region. SEABIRD will enroll more than 1,100 individuals including diversity in race, socioeconomic status, medical history and cognitive status....they found that measuring levels of several different forms of p-tau in blood over time may enable clinicians and researchers to track the stages of Alzheimer’s progression in people living with the disease.

Alzheimer's Risk Factors May Be Measurable in Adolescents and Young Adults (2020)

  • Early Adult BMI (but not Late Life BMI) Associated With Late Life Dementia Risk
  • "Hgher early adulthood (age 20-49) body mass index (BMI) was associated with higher late-life dementia risk."
  • "Relatively little is known about the role of early life BMI on the risk of Alzheimer and other dementias....a total of 5,104 older adults from two studies, including 2,909 from the Cardiovascular Health Study (CHS) and 2,195 from the Health, Aging and Body Composition study (Health ABC), [of whom] 18% were Black and 56% were women {were studied].
  • "For women, dementia risk increased with higher early adulthood BMI. Compared to women with normal BMI in early adulthood, dementia risk was 1.8 times higher among those who were overweight, and 2.5 times higher among those who were obese."
  • They found no association between midlife BMI and dementia risk among women.
  • "For men, dementia risk was 2.5 times higher among those who were obese in early adulthood, 1.5 times higher among those who were overweight in mid-life and 2.0 times higher among those who were obese in mid-life, in models also adjusted for late life BMI."
  • For both women and men, dementia risk decreased with higher late life BMI.
  • Adina Zeki Al Hazzouri, Ph.D. of Columbia University and colleagues found that high BMI in adulthood is a risk factor for dementia in late life. The researchers suggest that efforts aimed at reducing dementia risk may need to begin earlier in life with a focus on obesity prevention and treatment.

Funding Areas in AD/RD Research through the U.S. National Institute on Aging

NIA-Funded Active Alzheimer’s and Related Dementias Clinical Trials and Studies Dec. 2020

  • Every year, the U.S. Congress approves funding for research into the epidemiology of Alzheimer's Disease (AD) and related dementia, including Parkinson's disease (PD), Lewy body Dementia (LBD, Frontal Temporal Dementia (FTD), vascular dementia (VD) and mixed dementia (Alzheimer's with one or more other dementias). As of early 2021, funding for Alzheimer's and dementia related research at the National Institutes of Health (NIH) is $3.1 billion, following an additional $300 million increase for fiscal year 2021. This is more than double the amount budgeted as recently as 2016. Alzheimer's Impact. Movement
  • The National Institute on Aging (NIA) is currently supporting 272 active clinical trials on Alzheimer’s disease and related dementias. NIA’s active trials include: early-stage clinical drug development, late-stage clinical drug development, non-pharmacological interventions, clinical therapy development for neuropsychiatric symptoms of dementia, and care and caregiver interventions. For more information on each of these ares, see this December 2020 list with detailed links in each area: NIA Ongoing AD Clinical Trials

What is a Randomized Control Trial (RCT) or Double-Blind Trial and Why Does It Include a Placebo Group?

  • If you've read about "gold standard" clinical trials, often called RCTS, you may have wondered what makes them different from just giving some people an exercise program, a supplement, a brain-training app, mindfulness training, or a drug under study and then seeing how they do compared to their performance before the intervention. You may also have wondered why you would join a clinical trial if you might be given only a placebo. The NIA wants people to be well-informed about their participation and the reasons for decisions in clinical trials. Here's an excerpt from their website: NIA: Placebo in Clinical Trials
  • "In undertaking a clinical trial, researchers don’t want to leave anything to chance. They want to be as certain as possible that the results of the testing show whether or not a treatment is safe and effective. The “gold standard” for testing interventions in people is the “randomized, placebo-controlled” clinical trial. That means volunteers are randomly assigned—that is, selected by chance—to either a test group receiving the experimental intervention or a control group receiving a placebo or standard care. A placebo is an inactive substance that looks like the drug or treatment being tested...in many trials, no one—not even the research team—knows who gets the treatment, the placebo, or another intervention. When participants, family members, and staff all are “blind” to the treatment while the study is underway, the study is called a “double-blind, placebo-controlled” clinical trial.Randomized, placebo-controlled clinical trials (RCTs)
  • "In many trials, no one—not even the research team—knows who gets the treatment, the placebo, or another intervention. When participants, family members, and staff all are “blind” to the treatment while the study is underway, the study is called a “double-blind, placebo-controlled” clinical trial."
  • Note: The "arms" of a trial don't have to be 50% percent placebo and 50% intervention; the design is determined with the help of biostatisticians. Because researchers know the expected effects of a "placebo", the arms may be 2/3 on Intervention and 1/3 placebo, or 1/3 on 50 mg. day of Study Drug; 1/3 on 25 mg/day of study drug and 13 on placebo
  • "Test and placebo groups are equally important, as shown by the results of numerous clinical trials. For example, early research suggested that ginkgo biloba, an herbal supplement, might be effective in delaying dementia. To find out, the National Institutes of Health (NIH) sponsored a 6-year, Phase 3 clinical trial with more than 3,000 participants age 75 and older. At the end of the trial, scientists reported that they had found no significant differences in effect on dementia in adults who received ginkgo biloba or the placebo. This result was disappointing, but scientists gained a wealth of information to inform future research. Based on the results of this and other trials in people with Alzheimer’s, scientists have begun to test treatments in people at earlier stages of disease— that is, people who may have Alzheimer’s-related brain changes but no memory loss or other symptoms. Many researchers think that treatment earlier in the disease process may help prevent or delay dementia.

Underserved and Underrepresented Communities in ApoE 4/Alzheimer's Research

Forget Me Not: Alzheimer's and the Black/African-American Community

  • Click on the link above to watch a 3 minute video from UsAgainstAlzheimers/African-Americans Against Alzheimers to hear from family members, caregivers, journalists, and researchers about the need to raise awareness, engagement, support and participation in clinical trials with Black communities.
  • Alzheimer's is the 4th leading cause of death among older African Americans.
  • 20% of Americans with the disease are African Americans, and they bear 33% of its national cost.
  • Overall, Alzheimer's clinical trials only have 3% of Black participants. As one researcher notes: Recommendations are made on who participates in clinical trials. All communities need to be represented to have valid recommendations. That may be especially true for Apoe4 carriers who are Black, since it appears that the effects of APoE4 may be different within African populations and between African, Caribbean-African and African-American populations.

LatinosAgainst Alzheimer's: Latinos & Alzheimer’s Disease: New Numbers Behind the Crisis

  • "While Latinos make up 17% of the U.S. population, they make up less than 1% of participants in all National Institutes of Health clinical trials. Further, Latinos make up just 7.5% of research participants across the approximately 32 Alzheimer’s Disease Research Centers (ADRCs) funded by NIH. Latino volunteers are needed to help researchers understand and develop treatments and health interventions for AD that work for all ethnic groups.... Further, recruitment strategies and trial designs should better reflect the needs and realities of Latino communities."
  • Our Mind: Investigation About Alzheimer’s Disease in the Latino Community (video in English.
  • ¿Qué le pasa a mi memoria? (Video in Spanish.

Collaborative Approach for Asian Americans & Pacific Islanders Research & Education Registry

  • The Center on Aging: Connecting with Asian-American and Pacific Islanders About Dementia reports that "Asian Americans and Pacific Islanders (AAPI) are the fastest growing minority group in America.
  • Between 2010 and 2030, the AAPI older adult population is projected to increase by 145%.1 As this aging population rapidly increases, AAPI older adults face a public health crisis similar to older adults from other ethnic backgrounds, as age is the largest risk factor for Alzheimer’s disease. The prevalence and incidence of Alzheimer’s disease and related dementias within AAPI communities is not well understood.
  • Limited disaggregated research unveils that Vietnamese older adults have a disproportionately high prevalence of cognitive problems (16.6%), more than double the rate for Koreans at 7.6%. Native Hawaiians and Pacific Islanders have a higher risk of cognitive issues and activities of daily living impairments, which is two times the risk as compared to Chinese older adults."
  • NOTE: If you or someone you know is a member of the AAPI community, please share this National Institute on Aging (NIA)-sponsored registry link with them, so that this under-represented community may benefit from AD clinical research: Collaborative Approach for Asian Americans & Pacific Islanders Research & Education Registry

Genome-Sharing Resources

  • The Personal Genome Project at Harvard began in 2005 and is now a member of the Network of Personal Genome Projects that has grown to include researchers at many leading institutions around the globe. According to the PGP "Open data is a critical component of the scientific method, but genomes are both identifiable and predictive, so many studies don’t share their data. The PGP is a unique resource of public human data that allows open collaborative research on human genomes and biology. Donating your genome and health data to science is a great way to enable advances in understanding human genetics, biology, and health. We seek volunteers willing to donate diverse personal information to become a public resource."
  • OpenSNP "allows customers of direct-to-customer genetic tests to publish their test results, find others with similar genetic variations, learn more about their results by getting the latest primary literature on their variations, and help scientists find new associations."

NIH ClinicalTrials.gov: Learn About Clinical Trials

The NIH has a searchable database with information about clinical trials on many subjects, across many countries, including those funded by governments, academic research centers, non-profit organization, and private companies. You can get a good sense of what is involved in a clinical trial and what questions to ask if you volunteer to be screened for participation here: [https://clinicaltrials.gov/ct2/about-studies/learn NIH ClinicalTrials.gov: Learn About Clinical Trials

  • To see the wide range of clinical trials currently or soon-to-be recruiting participants, try this link, which is updated as of Feb. 2021: Clinical Trials Alzheimer's Trials Currently Recruiting Participants
  • If you'd like to search in your specific city or state, or by a certain condition (ex. Mild Cognitive Impairment, Healthy Volunteers, age range) or type of study (observational, interventional) use the Advance Search function here: Clinical Trials: Advanced Search Function
  • To find studies (of all types) in your country, state, province or region, click on Clinical Trials: Interactive Map Display and then on the location of interest (ex. clicking on the map of the U.S. will take you to a map showing the number of trials in each state. Clicking on Minnesota will bring up a list of all clinical trials in Minnesota. Note that these will include trials other than AD trials.)

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.