The Three Major APOE Human Alleles - Terminology

 

The Three Major APOE Human Alleles

 

Apo-E belongs to a family of fat-binding proteins called apolipoproteins. In the central nervous system, Apo-E is mainly produced by astrocytes and transports cholesterol to neurons^[8] via APOE receptors, which are members of the low density lipoprotein receptor gene family.^[9] Apo-E is the principal cholesterol carrier in the brain.^[10] Apo-E is required for cholesterol transportation from astrocytes to neurons.^[8] (from wiki)

 

The three major human alleles of APO-E (E4, E3, E2) arose after the primate-human split around 7.5 million years ago. These alleles are the by-product of non-synonymous mutations which led to changes in functionality. The first allele to emerge was APO-E4. (from wiki)

 

About 220,000 years ago, a cysteine to arginine substitution took place at amino acid 112 (Cys112Arg) of the APO-E4 allele, and this resulted in the E3 allele. Finally, 80,000 years ago, another arginine to cysteine substitution at amino acid 158 (Arg158Cys) of the APO-E3 allele created the E2 allele.^[15][13] (from wiki)

 

E4 allele has Cys at 112 and Arg at 158 with worldwide allele freq. = 13.7%

Polymorphism rs7412-C, rs429358-C (388C-526C)

rs429358 (C;C) is only APOE4/4

 

Substitution on APO-E4 allele 220,000 years ago was Cys112Arg resulting in:

E3 allele with Arg at 112 and Arg at 158 with worldwide allele freq. = 77.9%

Polymorphism rs7412-C, rs429358-T (or 388C>T or 388T-526C)

 

Substitution on APO-E3 allele 80,000 years ago was Arg158Cys resulting in:

E2 allele with Arg at 112 and Cys at 158 with worldwide allele freq. = 8.4%

Polymorphism rs7412-T, rs429358-T (or 526C>T or 388T-526T)

rs429358 (T;T) is APOE3/3, APOE2/3, or APOE2/2

rs7412 (T;T) is only APOE2/2 

rs7412 (C;C) is APOE4/4, APOE3/4, or APOE3/3

Posts from Alzheimer’s: Late and Early Onset, APOE-4 (the group is permanently paused)

 

A little bit of aluminum every day can lead to a large amount of accumulated aluminum in the brain. It is estimated that 4% of the aluminum you ingest today will still be in your body 50 years later

Getting Started 

1.You need to drink 3 to 4 cups of silica water to remove aluminum from your body. Spread your drinking throughout the day. If you do an activity where you sweat drink some silica water before starting.

 

2. Silica supplements will not remove aluminum as some do not have the form of silica needed to remove aluminum. OSA (orthosilicic acid) is the form of silica needed. Some silica supplements contain OSA but do not have enough OSA to remove aluminum. These supplements have been tested by my husband Dennis N Crouse who is a chemist. Please do not ask or post about silica supplements in this group.

 

3. This is called ‘Targeted Detox” as OSA only removes aluminum. OSA forms a tight bond with the aluminum which detoxifies the aluminum and also facilitates the elimination of aluminum from the body. I have information on targeted detox for mercury, lead and arsenic. Supplement that are either essential to or made by the body are used to detox. OSA is orthosilicic acid and is the form of silica found in mineral water.

 

4. Fiji water is not the only water that has enough silica to remove aluminum. There is a list of waters from all over the world that have enough silica to remove aluminum.  https://prevent-alzheimers-autism-stroke.com/2021/08/26/bottled-silica-waters-from-around-the-world/

 

5. For a more sustainable way of getting your silica water, there is a recipe for making your own silica water called Silicade. Dennis N Crouse (my husband) who is a chemist developed the recipe. Silicade has the same amount of OSA as Fiji water.  https://prevent-alzheimers-autism-stroke.com/silicade/

Preventing or Reversing Alzheimer's  3 prong approach

1.     Drink silica water to remove aluminum. 3 to 4 cups a day. Spread your drinking throughout the day. If you do an activity where you sweat drink silica water before the activity.

2. Take supplements, 'nootropics' to improve brain function. Daily augmentation with nootropics normally found in the body and regular periodic aerobic exercise have been demonstrated in human clinical trials to boost cognition and memory. Link to Crouse Protocol There is a table at the end of the write up. (examples of nootropics, PQQ, CoQ10) https://prevent-alzheimers-autism-stroke.com/2021/10/25/crouse-protocol-for-reversing-mci-and-ad/ 

3. Look for sources of aluminum and eliminate as many as you can. Cookware, baking powder (a major source), dyes in pharmaceuticals, foods and cosmetics, anti perspirants, antacids, most drip style coffee makers, drinking water that is treated with alum.

Aluminum is used as a anti caking agent in many food products. For example: grated parmesan cheese.

For the antacids you can look for ones that contain calcium carbonate and sodium bicarbonate. Antacids with calcium carbonate: Walgreens antacid white, Tums Natural, Equate, CVS natural (Look carefully at the labels as each company makes many different antacids)

https://prevent-alzheimers-autism-stroke.com/2021/10/04/sources-of-aluminum/

Link to anecdotal information from the facebook group and other sources

Some people with symptoms have seen improvement in 2 months. For others it can take up to 4 months. 

https://prevent-alzheimers-autism-stroke.com/alzheimers/

           Medication for Alzheimer’s speeds up the progression of Alzheimer's

ARICEPT AND OTHER CHOLINESTERASE INHIBITORS ACTUALLY INCREASE THE PROGRESSION OF DEMENTIA

Here is information about medications which are prescribed for Alzheimer's. If you or your loved one is on a Cholinesterase inhibitor (medications listed below) you may want to reconsider.

Aricept and other Cholinesterase inhibitors actually increase the progression of dementia. 

One study found 'The mean time to dementia was 30% quicker in the ChEI treated group than the untreated group'. I decided to make this post because in another Alzheimer's group a woman posted she forgot her Mom's Aricept medication for a few days and found her mother was better. I then searched the group and found two 50 year olds have started on this medication.

Here is an excerpt from Dennis' book: Increasing IQ, Cognition and COVID-19 Cure Rate with Essential Nutrients

 "Efficacy of Cholinesterase Inhibitors and Memantine

Many people with mild cognitive impairment (MCI) and mild Alzheimer’s disease (AD) are prescribed a cholinesterase inhibitor (ChEI). Those with moderate to severe AD (e.g., Mini-Mental State Examination [MMSE] scores below 15) are prescribed memantine, with in some cases a ChEI. Administration of a ChEI increases the concentration of acetylcholine by inhibiting its breakdown. These drugs treat some of the symptoms of MCI, such as memory loss, agitation, apathy, and psychotic symptoms including delusions, hallucinations, and disordered thought. Examples of ChEIs are:

• Galantamine (trade name Razadyne) is approved by the FDA for treatment of vascular dementia and mild to moderate AD. It enhances memory in brain-damaged adults544.

• Rivastigmine (trade name Excelon) is approved to for mild and moderate AD.

• Donepezil (trade name Aricept) is approved to treat all stages of AD.

A study was published in 2011 on the efficacy of these three ChEIs and memantine taken by patients diagnosed with MCI or mild AD. Approximately one-half of 392 MCI patients and two-thirds of 188 mild AD patients were APOE-4 carriers. Among the MCI patients 33.4% received only ChEIs, 11.7% received ChEIs and memantine, and 54.9% received neither. Among the 188 AD patients 38.9% received ChEIs, 45.7% ChEIs and memantine, and 15.4% neither817.

The patients with MCI were divided into three groups, only 22% of the non-treated group progressed to dementia, 43% of the ChEI treated group progressed to dementia, and 56% of the group treated with both memantine and ChEI progressed to dementia. Therefore, there is a greater risk of dementia among people taking these drugs. The mean time to dementia was 30% quicker in the ChEI treated group than the untreated group and 42% quicker for the memantine and ChEI treated group than the untreated group. Both MCI patients and AD patients who received ChEI treatment had a more severe decline in cognition than untreated patients. Therefore, these drugs may reduce symptomology of MCI and AD but both increase the risk of dementia and hasten the progression to dementia when compared with un-treated people (reference 817).

APOE4 - why are you at increased risk. It has to do with aluminum

People with the APOE4 gene produce more beta amyloid which forms neurotoxic oligomers that react with aluminum to form neurotoxic droplets (Nano droplets) of amyloid oligomers. These neurotoxic droplets are very stable and mobile in the brain and are “freezing” the amyloid in the oligomeric state. These beta amyloid oligomers are 10 times more neurotoxic than amyloid plaque.”

Here is link to the introduction of my husband's 4th book. It has information on APOE 4. There are graphs with information on risk based on APOE status. http://prevent-alzheimers-autism-stroke.blogspot.com/2022/03/finding-cause-and-potential-cures-for.html

My Rant: HAVING APOE 4/4 DOES NOT MEAN YOU WILL GET ALZHEIMER’S!

I am saddened, angry and frustrated when I read posts from people with APOE 4/4 (or 3/4) who are scared of getting Alzheimer’s, and enrolling in studies that target beta amyloid and Tau. This shouldn’t be and doesn’t have to be the case.

I am hopeful the information provided in this group from my husband’s writing has and will decreased people’s fear. Simply put aluminum is the cause of Alzheimer’s and removing aluminum by drinking silica water and reducing your exposure to aluminum will prevent you from getting Alzheimer’s. I am angry because the pharmaceutical industry and the Alzheimer’s association pray on people’s fear so they can get people into drug trials. Drug trials targeting Beta amyloid over the past 2 decades have failed but yet these trials continue. They are now targeting younger people stating if we remove the beta amyloid earlier by drugs we can prevent Alzheimer’s. This won’t happen because aluminum makes the beta amyloid toxic. This is explained in more detail in my husband’s 4th book Rung 6. For example: Beta-Amyloid-42 is a Biomarker of AD. “Aluminum containing Ab-42 oligomers (0.5mM) are more neurotoxic than aluminum-free Ab-42 oligomers (0.5mM)53 .”   http://prevent-alzheimers-autism-stroke.blogspot.com/2022/03/finding-cause-and-potential-cures-for.html

Myths I have encountered 

"A few things happened this week that got me thinking about some of the myths I encountered when I was first learning about Alzheimer's and how much my perspective and knowledge base about the disease has changed over the past 10 years.

I have learned that:

1. Memory loss is not an inevitable part of aging (senior moments are not normal)

2. Only a small percentage of Alzheimer's is genetic

3. Having the APOE-4 gene makes a person at higher risk for Alzheimer's but doesn't mean you will get Alzheimer's

4. Of course the most important thing I learned is Aluminum is the cause of Alzheimer's and the OSA (silica) in drinking water can effectively remove aluminum from the body

5. Beta Amyloid is not the cause of Alzheimer's and this is why drugs targeting Beta Amyloid have failed over the past 2 decades.

6. There is a 'treatment' for Alzheimer's. The progression of the disease can be stopped and a person's cognition can be improved.

7. Alzheimer's can be prevented. A world without aluminum would be a world without Alzheimer's. 

Link to the Crouse protocol  https://prevent-alzheimers-autism-stroke.com/2021/10/25/crouse-protocol-for-reversing-mci-and-ad/

PQQ and CQ10

Here is information about PQQ (miracle grow for the brain). You want to take this in combination with CoQ10. PQQ stimulates both neurite growth and mitochondrial biogenesis. CoQ10 improves the energy efficiency of mitochondria. PQQ taken together with CoQ10 improves cognition in the ageing brain. Below is an excerpt from my husband's first book. and a link to more information on PQQ.

There are six reasons to take PQQ:

• PQQ protects mitochondria from oxidative stress due to nitric oxide (NO) produced by the brain’s glial cells in response to aluminum. PQQ lowers NO production by inhibiting the expression of genes responsible for the production of inducible nitric oxide synthase (iNOS)121,261-263 . With the help of glutathione PQQ also acts as a stable antioxidant264,265 .

• PQQ promotes the generation of new mitochondria, called mitochondrial biogenesis266 that increases energy efficiency of mitochondria267 .

• PQQ increases production of nerve growth factor (NGF) in the mitochondria268 that results in increased neurite growth and improved memory269,270 .

• PQQ when taken before and after a stroke can help to avoid vascular dementia by reducing memory impairment due to lack of oxygen271,272 . Since we don’t know when a stroke might occur, taking PQQ daily is advised.

• PQQ partially inhibits Aβ oligomer formation from Aβ peptides, one of the hallmarks of AD273 .

• PQQ binds to α-synuclein preventing formation of aggegates274. Formation of αsynuclein aggregates is believed to be the first step in Lewy body formation leading to Lewy body dementia (see Appendix I). 

BAKING POWDER A Major SOURCE OF ALUMINUM

Baking powder is a major source of aluminum and you should look for an aluminum free baking powder or make your own. Recipe to make your own. There is 48,600 mcg/tsp of aluminum in baking powder.

1 part Baking Soda

2 parts Cream of Tartar

(optional) 1 part Corn Starch (so it doesn't cake) Store in an airtight container 

You may need a shifter when using this baking powder. 

Here are some baked goods you want to make sure the baking powder is aluminum free. I am a baker and some of these I was surprised to learn could contain aluminum laden baking powder.

Tortillas, biscotti, scones, corn bread (a lot of baking powder), some muffin recipes, some fried chicken, some cookies (most recipes use baking soda), some donuts, pancakes, and cakes. I am sure I have missed a few.

Here is an excerpt from a letter I give to bakeries

"A daily diet of pancakes, waffles, muffins, or biscuits increases the risk of Alzheimer’s by 760%. This is because most commercial baking powder contains sulfate, phosphate, and pyrophosphate salts of aluminum used to acidify baking soda during baking.

Muffins and other baked goods made with aluminum containing baking powder are beyond TOXIC for your brain!!!! For instance, muffins made this way can contain 20 mg of aluminum per muffin. These muffins made with baking powder containing aluminum have 200 times higher aluminum levels than the safe aluminum level in a quart of drinking water. A little bit of aluminum every day can lead to a large amount of accumulated aluminum in the brain. It is estimated that 4% of the aluminum you ingest today will still be in your body 50 years later."