Aluminum as a causal factor of Alzheimer's

Excerpt from my book Silica water the Secret to Healthy Longevity in the Aluminum Age available on Amazon

https://www.amazon.com/Dennis-N.-Crouse-Ph.D./e/B01LFW4782

My wife Laurie Adamson has set up a facebook group.  Alzheimer's: Late and Early Onset, APOE4 https://www.facebook.com/groups/509038829797535/

Alzheimer’s Disease

My interest in silica water was inspired by a desire to help my mother slow or possibly reverse the progression of her Alzheimer’s disease.  I read Dr. Christopher Exley’s work on daily silica water treatments improving cognition in some Alzheimer’s patients and hoped this might work for my mom^73,78.  My research on Alzheimer’s disease and ways to prevent it are summarized in my book “Prevent Alzheimer’s, Autism, and Stroke with 7 Supplements, 7 Lifestyle Choices, and a Dissolved Mineral”¹.  The dissolved mineral mentioned in the title refers to the water soluble silica called orthosilicic acid (OSA). 

Alzheimer’s disease is a terminal disease that slowly erases ones memory and identity. In the U.S.A. we are witnessing an exponentially growing epidemic of Alzheimer’s (see Figure 22). Currently 700,000 people in the U.S.A. die every year from Alzheimer’s making it the sixth leading cause of death. It is estimated that 1 out of 3 people in the U.S.A. over 80 have Alzheimer’s.

But Alzheimer’s is not an inevitable part of ageing. There are locations in the world, such as Japan and Okinawa, with a longer life expectancy than the U.S.A. and where there is much lower percentage of people dying from Alzheimer’s than in the U.S.A. (see Table 24). These areas of the world have on average much higher levels of OSA in their drinking water than the U.S.A.

In Table 24 both male and female survival rates are the percentage of people 60 to 79 who will make it to age 90 in each location.  This table shows that both male and female survival rate to age 90 is higher in Mainland Japan (e.g. Honshu) and Okinawa than the U.S.A. The table also shows the Alzheimer’s death rate in the U.S.A. compared with Mainland Japan and Okinawa is inversely correlated with average ppm OSA in drinking water. This OSA rich water is used for both drinking and crop irrigation.

The seven largest epidemiology studies looking at the link between aluminum in drinking water and the risk of Alzheimer’s have found over 100ppb of aluminum in drinking water increases the risk of Alzheimer’s¹. In addition several of these studies found a dose response relationship between the concentration of aluminum and the risk of Alzheimer’s^238-246. The good news is that one long-term study found that OSA greater than 18ppm in drinking water lowered the risk of Alzheimer’s^246,247. A second long-term study also confirmed that women over 75 drinking OSA rich water 19ppm to 57ppm were less likely to be diagnosed with Alzheimer’s and had higher cognitive performance than women drinking water with less than 19ppm OSA²⁴⁸.

Biomarkers for Alzheimer’s

Three genes and an environmental factor (i.e. aluminum) have been linked as causal factors to Alzheimer’s disease. There are three types and two sub-types of Alzheimer’s disease (AD):

·         Sporadic AD is the most common type (98-99% of AD patients) with two sub-types:

o   Those without e4 allele of APOE gene (44% of sporadic AD patients in U.S.A.)²⁴⁹

o   Those with one or more copies of e4 allele of the APOE gene (56% of sporadic AD patients in U.S.A. and 50% of early-onset AD patients)^249,250

·         Familial AD with presenilin 1 or presenilin 2 genes (1-2% of AD patients in U.S.A. and 35 to 75% of early-onset familial AD patients)²⁵¹

·         Occupational AD is the least common with at least one case of early-onset AD due to aluminum reported in the scientific literature²⁵²

Twenty percent of people in the U.S.A. have one or more copies of the e4 allele of the APOE gene. These people have a 50% greater than normal chance of having sporadic AD. This makes the APOE-e4 gene a potential causal factor of AD but not a reliable biomarker for AD (see “Aluminum and the Risk of AD in People with the APOE-e4 Gene” at the end of this chapter). People with the presenilin genes are almost certain of having familial AD, making the presenilin genes biomarkers for AD.      

In addition to these genetic biomarkers, there are three biomarkers common to all types of AD:

·         Aluminum hotspots in the frontal and entorhinal cortex and hippocampus of the brain

·         Neurofibrillary tangles (NFTs) of tau protein in the frontal cortex of the brain

·         Beta-amyloid (Ab) plaque in the frontal cortex of the brain

All of these biomarkers are visible microscopically in the autopsied brain with appropriate stains.  The NFT’s and Ab plaque were discovered in 1906 by Doctor Alzheimer and the aluminum hotspots were first noted in 1973 by Crapper²⁵³.  Recently there have been procedures developed for analyzing for these biomarkers in living patients (i.e. in vivo) by sampling cerebrospinal fluid or serum^254-256 or completely non-invasively by PET or MRI scans of the brain^257,258.  Retinal fluorescent lifetime and optical imaging of the eye has also been used to screen for some of these biomarkers^259-262.

Warning: In vivo detection of genetic and non-genetic biomarkers of Alzheimer’s is in its infancy and suffers from high levels of false-positives and false-negatives. In addition, a percentage of the population can be resilient to the effects of some biomarkers. For example, 23.2% of a group of 966 people in two combined studies who had both a brain autopsy after death and comprehensive cognitive testing proximate to death were found to be resilient to beta-amyloid (Ab) plaque in their brains. The 224 people found to be resilient had a significant amount of Ab- plaque in their brains but no symptoms of Alzheimer’s disease and were therefore without an Alzheimer’s diagnosis at the time of death^263,264.        

Aluminum as a Causal Factor of Alzheimer’s

From aluminum analysis of the brains of those who died of sporadic AD, familial AD, and occupational AD, it has been concluded that median levels of aluminum in excess of 2.0mcg per gram dry weight of brain across all four main lobes is both a common characteristic of AD and a contributor to its etiology²⁶⁵. In 2005 aluminum levels in specific brain regions in three AD patients and three non-demented controls was measured²⁶⁶.  The data in the Table 25 shows regions of the brain where there were aluminum hotspots. In these regions aluminum is preferentially absorbed at higher levels in AD patients than non-demented controls²⁶⁶.

In 2011 Rusina et al. measured both aluminum and mercury in the hippocampus and associated visual cortex of 27 controls and 29 histologically-confirmed AD cases.  There was a four-fold increase in aluminum levels in the hippocampus of the AD cases versus the controls.  There was no difference in mercury levels between the AD cases and controls²⁶⁷. An amount as high as 8mcg/g of aluminum per gram dry weight of brain tissue has been found in the inferior parietal lobe of AD patients²⁶⁸. Hotspots in human brains with AD typically are in excess of 4mcg/g dry weight of brain tissue²⁶⁸.  They contain a large number of NFTs or large pyramidal cells with high levels of aluminum.  Hotspots are not found in non-demented age-matched controls²⁶⁸.  

It has been shown that a causal factor of all types of AD is environmental and not genetic¹. Out of all environmental factors considered, only aluminum experimentally triggers all major histopathological events associated with Alzheimer’s²⁶⁹. The “hotspots” in the brain where the highest levels of aluminum were found include the hippocampal complex, entorhinal cortex, and frontal cortex²⁶⁶. These areas of the brain are all important for memory.  Impaired memory is the core clinical feature of AD. The entorhinal cortex had the highest overall aluminum levels, is amongst the earliest regions of the brain to develop NFTs, and is ultimately the most damaged region of the brain in AD^270-273.

Some brain atrophy in the hippocampal complex and the frontal cortex (i.e. 0.3-0.6%) is common with age in healthy adults²⁷⁴. In 2009 Fjell et al. studied brain atrophy in people 60-91 years old.  The study included 142 healthy participants and 122 with AD.  The four areas of the brain found to significantly atrophy during one year in AD patients were the same areas found to be hotspots for aluminum accumulation. Also the rate of atrophy is much higher in AD brains than in healthy adult brains as shown in Table 26²⁷⁵.  Of course even healthy brains have accumulated some aluminum and that could account for the atrophy observed in the controls.

There is ample evidence that aluminum is a causal factor of Alzheimer’s, while there is evidence that Ab plaque and NFTs are merely symptoms of aluminum accumulation in the brain¹. Currently billions of dollars are being invested in research to develop drugs for removal of Ab plaque and NFTs from the human brain. Even if successful, these drugs will only provide palliative relief as they are only addressing symptoms and not a causal factor of Alzheimer’s. I am not aware of any research dollars being currently spent on how to remove the causal factor - aluminum from the human brain. This is sadly ironic because on earth we have been blessed with low cost silica to reverse aluminum accumulation.

The Fly in the Ointment

Are the potential profits from future Alzheimer’s drug sales or the current profit from aluminum sales preventing the evaluation of low cost and more natural solutions to Alzheimer’s, such as adding supplemental silica to drinking water?  Silica as a treatment does not fit the drug company’s model of a successful drug (i.e. it is not a patentable pill or an inoculation that provides quick relief). Silica supplementation as a drinking water treatment needs to be both implemented by public health departments and embraced as an additive to domestic bottled water. 

Obfuscation, paid for by the aluminum industry, has put aluminum research temporarily on hold. The aluminum industry has paid some scientists to publish articles on why aluminum does not cause Alzheimer’s. Typically these articles point out that people with kidney failure on hemodialysis have high levels of aluminum in their blood but don’t have a high incidence of Alzheimer’s disease.  They fail to mention that people with kidney failure can’t eliminate both OSA and aluminum by urination and have high levels of both of them in their blood as shown in Table 27^276,277.

With a working blood-brain-barrier, the OSA keeps the aluminum in the brain’s cerebrospinal fluid at safe levels (i.e. 3-7mcg/liter) as shown in Table 27²⁷⁶. Approximately 4% of hemodialysis patients have a damaged blood-brain-barrier and die in a year or less due to aluminum quickly accumulating in the brain causing dementia (i.e. aluminum encephalopathy) in spite of high levels of silica. Since Alzheimer’s disease takes 5 to 20 years before symptoms develop, hemodialysis patients with a damaged blood-brain-barrier die of aluminum encephalopathy long before they can develop Alzheimer’s.

In 1998 a group under the leadership of J.D. Birchall found that high silica levels in the blood of hemodialysis patients lowered their aluminum levels²⁷⁸. They concluded:

 “Further work needs to confirm a preventive role for silicon in the accumulation and subsequent toxicity of aluminum in dialysis patients.”²⁷⁸

For those hemodialysis patients with a working BBB, the silica and aluminum form particles of HAS at the BBB preventing both Alzheimer’s and high levels of aluminum in their brains²⁷⁹.

Aluminum and the Risk of AD in People with the APOE-e4 Gene

The APOE-e4 gene increases the concentration of beta-amyloid peptide in the brain and has been linked to a higher risk of AD.  The e4 allele of the APOE gene was introduced into the human population at least 1.5 million years ago²⁸⁰. The reproductive advantage of carrying the e4 allele was to promote human fertility in highly infectious environments in spite of its adverse effects on late onset diseases (i.e. an example of antagonistic pleiotropy)²⁸¹. Because of this reproductive advantage the e4 allele frequency slowly increased during the last 1.5 million years with currently approximately 14% of the worldwide population carrying the e4 allele²⁸⁰.

Because of improved hygiene and vaccines there is no longer a reproductive advantage to those that carry the e4 allele. In the absence of a reproductive advantage, the e4 allele frequency in the worldwide human population is not predicted to change (e.g. the Hardy-Weinberg principle).

Therefore the recent exponential growth of AD is not due to an exponential increase in e4 allele frequency. Instead the exponential growth of AD is due to a newly introduced environmental chemical that potentiates APOE-e4 making one of its protein products or their derivatives, such as oligomeric beta-amyloid peptide, more neurotoxic. This was proven to be the case by Denise Drago in 2008 when she tested a variety of metal ions (e.g. aluminum, iron, zinc, and copper) and found that only aluminum when bound to the oligomeric beta-amyloid peptide resulted in significantly increased neurotoxicity²⁸².

Aluminum is a causal factor of AD in people with and without the e4 allele of the APOE gene, but in those with this allele there is more oligomeric beta-amyloid for aluminum to toxify. For this reason usually those with the APOE-e4 gene have a higher risk of AD than those without the e4 allele. But what if there is an exception? What if there is an undiscovered Blue Zone on earth where people with the APOE--e4 gene had the same risk of AD as those without the APOE--e4 gene? What if people in this undiscovered Blue Zone drank OSA rich water and ate an OSA rich diet that lowered their aluminum body-burden to the point where they were protected from the APOE-e4 gene?

The Exception – Ibadan, Nigeria an Undiscovered Blue Zone

The exception to APOE-e4 being a casual factor of AD is the Yoruba people of Ibadan, Nigeria who coincidentally have the same e4 allele frequency as people in the U.S.A. From 1992 to 2006 the APOE gene was genotyped in 2,245 elderly Nigerians living in the city of Ibadan who were also clinically diagnosed. Surprisingly, in contrast with other populations, the e4 allele in the Yoruba people was not significantly associated with AD or dementia²⁸³.

The Yoruba people living in Ibadan are in general in better health than people living in the U.S.A. Age-matched annual incidence rates of both dementia and AD were found to be 2.4 and 2.2 times lower respectively, in a longitudinal study of a cohort of 2,459 elderly Yoruba people living in Ibadan versus a cohort of 2,147 elderly African-Americans living in Indianapolis, Indiana²⁸⁴.  In addition, these elderly Yoruba people have lower incidence of vascular disease and vascular risk factors including hypertension than does the age matched cohort of elderly in the U.S.A.²⁸³.   

OSA in Ibadan’s Drinking Water

Ibadan, Nigeria has a community water system that distributes water from the Eleyele reservoir. Tap water sampled at 11 sites across the distribution system indicated the water contained OSA at 22.4 to 25.6ppm²⁸⁵. This level of OSA in drinking water is approximately the same as average drinking water on mainland Japan (e.g. 26ppm) and more than twice the level of U.S.A. drinking water (e.g. 11ppm).  This more than 2-fold increase of OSA in drinking water is associated with a more than a 10-fold lower rate of death due to AD in Japan versus the U.S.A. (see Table 9).

It is not surprising that both the Yoruba people of Ibadan and Japanese living on mainland Japan both have lower incidence rates of AD than people in the U.S.A., since OSA in drinking water lowers the body-burden of aluminum, a causative factor of AD. It is also not surprising that among the Yoruba people of Ibadan the e4 allele was not significantly associated with AD or dementia, since without a body-burden of aluminum there is no increase in neurotoxicity of oligomeric beta-amyloid. This is the peptide that occurs in higher than normal levels in those people with the APOE-e4 gene.   

OSA in Ibadan’s Food

Nigeria is the leading worldwide producer of cassava with annual production of 45 million metric tons²⁸⁶. Cassava, the most important dietary staple in Nigeria, is a tuber whose skin is very rich in OSA^286,287. This makes cassava one of the richest vegetable dietary sources of silicon as OSA (e.g. approximately 270mg of silicon per 100 grams of cassava with skin that is equivalent to 920mg of OSA per 100 grams – see Table 23)^286,287.

The cassava root is toxic if not treated properly. Although cassava can be peeled with some difficulty, the tuber is usually cut into pieces with the skin on, dried, and fermented, in order to eliminate toxicity, and finally converted into three main foods by the Yoruba people²⁸⁸.

Gari – granular cassava flour with a ferment flavor and a slightly sour taste is eaten in stews and soups and served with fried fish. Gari is also used as a snack when mixed with milk and sugar.

Fufu – cassava flour mixed into a paste with hot or cold water is ranked next to gari as an indigenous food of the Yoruba people. 

Lafun – fibrous powdery form of cassava that is made into dough with boiling water.

The Yoruba people of Ibadan are a living example of how increased dietary OSA in their drinking water and food can lower the aluminum toxification of the oligomeric beta-amyloid peptide. This is the peptide that occurs in higher than normal levels in those people with the APOE-e4 gene. By following the example of the Yoruba people of Ibadan and increasing dietary OSA by consuming OSA rich drinking water and OSA rich food, the risk of AD is significantly decreased in everyone either with or without the APOE-e4 gene. 

Silica Water Protects Amyloid Beta Regulation

Why are annual incidence rates of both dementia and AD 2.4 and 2.2 times lower respectively in Ibadan, Nigeria than in the U.S.A.? The answer is OSA in the drinking water and food of Ibadan’s inhabitants protects amyloid beta (b-amyloid) regulation in their brains. Amyloid beta is a 36-43 amino acid peptide that is neurotoxic causing inflammation of neurons that can result in cellular death. Excess amyloid beta can also result in plaques in the brain that are a hallmark of Alzheimer’s disease (AD). Due its neurotoxicity amyloid beta is normally regulated in the brain. Amyloid beta regulation involves not producing too much amyloid beta and quickly degrading the amyloid beta that is produced to non-toxic fragments.  Aluminum interferes with both of these processes. Drinking OSA rich water and eating OSA rich vegetables facilitates aluminum excretion, thereby protecting amyloid beta regulation.

Amyloid beta is made enzymatically in the brain by a series of enzymes that cleave off chunks of amyloid precursor protein (APP).  b-secretase 1 (BACE-1) is one of the enzymes involved in making amyloid beta.  Aluminum epigenetically increases expression of b-secretase favoring the production of more amyloid beta^289,290.

Oligomers of amyloid beta (dimers, trimers, tetramers, etc.) are neurotoxic. Aluminum complexes of these amyloid beta oligomers are spherical droplets that are even more neurotoxic than amyloid beta oligomers²⁸². Aluminum “freezes” the amyloid beta oligomer by inhibiting its further degradation to smaller fragments²⁹¹.  The rate-limiting step in the degradation of amyloid beta is catalyzed by the enzyme neprilysin.  Aluminum epigenetically decreases expression of neprilysin that favors more amyloid beta in the brain^289,290.

Drinking OSA rich water and eating OSA rich vegetables decreases aluminum in the brain and restores amyloid beta regulation. In addition OSA prevents amyloid beta oligomers from becoming more neurotoxic. Treatment for high levels of amyloid beta in the brain can also be done with aerobic exercise, and sleep.  Aerobic exercise for 30 minutes increases the level of somatostatin in the brain that in turn decreases amyloid beta by increasing the activity of neprilysin¹.  Aerobic exercise also increases hippocampal volume²⁹².  In addition, sleep increases somatostatin expression and facilitates the purging of amyloid beta from the brain^1,293.

Conclusion of Alzheimer’s Disease - Alzheimer’s disease is the most common cause of dementia in the world.  In Okinawa there is 52% less dementia than in Mainland Japan (i.e. Honshu) and 96% less dementia than in the U.S.A. (see Table 9). In Ikaria there is 25% less dementia than on mainland Greece.  These Blue Zones have less dementia due to higher levels of OSA in their drinking water and food. This OSA facilitates the elimination in urine and sweat of accumulated aluminum in the people’s brains.

Aluminum is a neurotoxin that kills neurons in regions of the brain responsible for memory. In addition, aluminum causes neurodegeneration and brain atrophy in these same regions. Atrophy in these brain regions is seen in those suffering with Alzheimer’s disease. There is ample evidence that aluminum is a causal factor of Alzheimer’s¹. In spite of this scientific evidence, the U.S.A. Alzheimer’s Association, U.S.A. aluminum industry, and U.S.A. biopharmaceutical industry all actively deny the validity of this evidence establishing aluminum as a casual factor. In addition they have failed to recognize the connection between OSA and aluminum detoxification as a preventative for Alzheimer’s.

Removing aluminum from the human brain with daily OSA ingestion as a method of preventing and reversing Alzheimer’s disease is based upon scientific evidence^{73,78, 246-248}. The information in this book on how silica increases longevity also provides evidence that terminal diseases including Alzheimer’s can be prevented and reversed with OSA in drinking water and food. There is also anecdotal evidence that daily OSA ingestion reverses Alzheimer’s. For instance my mother at age 92 has now healed her brain and reversed her Alzheimer’s symptoms by daily drinking Fiji silica water (for details see Chapter 3 – Marion Iowa a Future Blue Zone).