Aluminum and its probable etiological association with neurodegenerative diseases
It has been proven beyond reasonable doubt that aluminum accumulation in the brain is a major etiological factor for the development of neurodegenerative diseases such as Alzheimer’s disease (AD), multiple sclerosis (MS) and Autism (ASD). Aluminum exposure has markedly increased over the past several decades after the commencement of a secret atmospheric geoengineering, aka, solar radiation management (SRM) program which became global in roughly 1992-1995. Prior to that time, the major source of aluminum toxicity in humans was from so-called “vaccine” injections where aluminum is used as an adjuvant/excipient. A less important environmental factor has been through the ingestion of aluminum containing dietary products/sources. This represents a massive crime against humanity.
Several potential treatments have been developed which can ostensibly be used for those with aluminum induced/associated neurodegenerative diseases, including, IV EDTA in combination with Cellfood (a proprietary formulation of a super energized mineral concentrate, including dissolved oxygen, trace minerals, plant source amino acids, and enzymes which allegedly provides significant antioxidant activity), the ingestion of Silicon containing water and physical exercise. These should all be further studied in a systematic way. It is not an exaggeration to acknowledge that without aluminum accumulation in brain tissue, there would be no Alzheimer’s disease. The catalyst for the development of AD is, invariably, the aluminum content in the brain and how effectively the brain responds to/copes with the aggregate aluminum burden.
A plethora of relevant/important scientific papers have appeared over the past two decades including:
Aluminum Should Now Be Considered a Primary Etiological Factor in Alzheimer’s Disease, (2017).
Aluminium involvement in neurotoxicity, (2014).
Exley C (2014) What is the risk of aluminium as a neurotoxin? Expert Rev Neurother 14:, 589–591.
Mirza A, King A, Troakes C, Exley C (2016) The identification of aluminum in human brain tissue using lumogallion and fluorescence microscopy. J Alzheimers Dis 54:, 1333–1338.
Efficacy of chelation therapy to remove aluminium intoxication, (2015).
EDTA Chelation Therapy in the Treatment of Neurodegenerative Diseases: An Update, (2020).
Readers are encouraged to evaluate the following paper:
Exley, C., Clarkson, E. Aluminium in human brain tissue from donors without neurodegenerative disease: A comparison with Alzheimer’s disease, multiple sclerosis and autism. Sci Rep 10, 7770 (2020).
Abstract
A burgeoning number of studies are demonstrating aluminium in human brain tissue (for example, see Mirza et. al., 2016, above). While research has both quantified and imaged aluminium in human brain tissue in neurodegenerative and neurodevelopmental disease there are few similar data for brain tissue from non-neurologically impaired donors. We have used microwave assisted acid digestion and transversely heated graphite furnace atomic absorption spectrometry to measure aluminum in twenty brains from donors without recognizable neurodegenerative disease. The aluminium content of 191 tissue samples was invariably low with over 80% of tissues having an aluminium content below 1.0 μg/g dry weight of tissue. The data for these control tissues were compared with data (measured using identical procedures) for sporadic Alzheimer’s disease, familial Alzheimer’s disease, autism spectrum disorder and multiple sclerosis. Detailed statistical analyses showed that aluminium was significantly increased in each of these disease groups compared to control tissues. We have confirmed previous conclusions that the aluminium content of brain tissue in Alzheimer’s disease, autism spectrum disorder and multiple sclerosis is significantly elevated. Further research is required to understand the role played by high levels of aluminium in the etiology of human neurodegenerative and neurodevelopmental disease.
Introduction
Human exposure to aluminium is burgeoning and its entry into and presence within the human body is inevitable1,2,3. There is no ‘aluminium homeostasis’4. The bioinorganic chemistry of aluminium dictates that it will ‘piggy-back’ upon essential biochemistry and it is such adventitious interactions that determine its fate in the human body. The brain is a target tissue for accumulation of aluminium5,6. Long-lived neurons provide intracellular pools, such as citrate, ATP and glutamic acid, where aluminium can remain complexed without necessarily disrupting cellular biochemistry7. Aluminium is neurotoxic and is found in brain tissue in extracellular milieu associated with neuropathology including senile plaques and neurofibrillary tangles in Alzheimer’s disease8,9. While there is no longer any debate as to the presence of aluminium in human brain tissue, there remains the question of how much aluminium in brain tissue is too much10. A number of recent studies have provided data on aluminium content in brain tissue in Alzheimer’s disease11, multiple sclerosis12 and autism13. The quantitative data, supported by aluminium-specific imaging, are invariably reported as being high, higher than expected. However, data on the latter, true control data are extremely rare. Brain banks have themselves struggled with the concept of what constitutes a true control14. We asked one such brain bank to identify a set of donor brain tissues that could act as a control for brains affected and diagnosed with a neurodegenerative disease. The majority of control brains available through brain banks are from older donors and so most still show some signs of age-related degeneration. Herein we have measured the aluminium content of twenty control brains where in each case there was no overt neurodegeneration, no diagnosis of a neurodegenerative disease but some age-related changes in the older donors. We have then compared these data, with data measured under identical conditions, for donors having died with diagnoses of Alzheimer’s disease, multiple sclerosis and autism.
Results
Control brain tissues
The aluminium content of all tissues ranged from 0.01 (the limit of quantitation) to 9.28 μg/g dry wt. (Table 1). The majority of tissues (150 out of 191) were below 1.00 μg/g dry wt. though 28, 6 and 7 tissues were in the range 1.00–1.99, 2.00–2.99 and ≥3.00 μg/g dry wt. respectively. The aluminium content of each lobe (mean and SD) were 1.03 (1.64), 1.02 (1.27), 0.95 (0.88), 0.77 (0.92) and 0.51 (0.51) μg/g dry wt. for frontal, temporal, parietal, occipital and cerebellum respectively. There were no statistically significant differences between aluminium content and age (p-value = 0.7656) or gender (p-value = 0.4005) and even though the cerebellum had the lowest content of aluminium, there were no statistically significant differences between any of the five brain regions (p-value = 0.2488; Table 2; Fig. 1).
Comparison with disease groups
We compared control brain data with each of four treatment groups, namely sporadic Alzheimer’s disease (sAD), familial Alzheimer’s disease (fAD), autism spectrum disorder (ASD) and multiple sclerosis (MS). The descriptive statistics for each of these groups are shown in Table 3. The sAD group is actually composed of both control donors and donors diagnosed with sporadic Alzheimer’s disease, an approximate 50/50 split, see later for a more detailed explanation of this. In addition, this group has been analyzed according to how negative values in the original data set are dealt with, for example; sAD- sporadic Alzheimer’s disease (including negative values); sAD+- sporadic Alzheimer’s disease (negative values adjusted to LOQ); sAD– - sporadic Alzheimer’s disease (negative values excluded).
Table 3 Descriptive statistics for the different groups under comparison.
Treatment group (sAD; sAD–; sAD + ; fAD; ASD; MS) was the only factor that consistently affected the aluminium content of donor brain tissue. This was the case for all statistical analyses carried out including; when units were unweighted observations or means of individuals; for both adjustments sAD+ and sAD–; for truncation of outliers; parametric or non-parametric procedures (Table 4). The aluminium content of brain tissue in the control group was significantly lower than sAD (P = 0.0006), fAD (P = 0.0020), ASD (P = 0.0123) and MS (P < 0.0001) (Fig. 2).
Discussion
We present the first comprehensive data set for the aluminium content of brain tissue in donors without a diagnosis of neurodegenerative disease. All donors fulfilled recently revised criteria for control brain tissues14. Approximately 80% of measured tissues have an aluminium content below 1.0 μg/g dry wt. (Table 1). There are some anomalies, 6 out of 191 tissues have an aluminium content ≥3.00 μg/g dry wt., and these are worth future investigation to identify possible neuropathology. There was no statistically significant relationship between brain aluminium content and age of donor and this observation is contrary to a previous investigation of brain aluminium in a neurologically normal population15. An explanation may be that herein only two out of twenty donors were below 66 years old. The data do support a conclusion that a high content of brain aluminium is not an inevitability of ageing.
When we compared the new control data set with data produced in an identical manner in donors dying with diagnoses of sporadic Alzheimer’s disease (sAD)16, familial Alzheimer’s disease (fAD)11, autism spectrum disorder (ASD)13 and multiple sclerosis (MS)12 all of these disease groups had significantly higher brain aluminium content. The differences were always highly significant regardless of the method of statistical analysis (Table 4). The largest disease group, designated as sAD, was actually composed of approximately equal numbers of donors previously described by a brain bank as controls and donors diagnosed with sAD. Unfortunately, information discriminating between control and sAD donors was not made available to us17. However, the observation that the aluminium content of brain tissue in this group as a whole was significantly higher than the similarly aged control group emphasized the likelihood that brain aluminium content is increased in sAD. The data for the control group demonstrate that high content of brain aluminium is not an inevitability of living in the aluminium age. All disease groups had significantly higher brain aluminium content than the control group in spite of low numbers of donor brains, for example only 5 in ASD, and high variability within measured tissues. The disease groups, sAD, fAD, ASD and MS shared the characteristics of significant focal deposits of aluminium throughout all main lobes of the brain and associated neuropathology and neurodegeneration. Quantitative data, even when complemented with high quality aluminium-specific fluorescence microscopy18, do not directly confirm a role for aluminium in each of these diseases. However, since there is no debate as to the neurotoxicity of aluminium in humans19,20,21, such data do implicate aluminium in disease aetiology. Animal models of aluminium intoxication reproduce the neuropathology’s and neurodevelopmental effects of human neurodegenerative disease, if not the diseases per se22,23. Cell models and in vitro studies demonstrate mechanisms of aluminium toxicity known to be involved in human neurodegenerative disease24,25. Perhaps the information that is still missing from our understanding of aluminum’s role in each of the diseases compared herein is how much aluminium is too much in human brain tissue10. The comparison we have made herein between control brain tissue showing no signs of neurodegenerative disease and the disease groups sAD, fAD, ASD and MS is beginning to answer this question. Only further measurements on more donor brains will enable a definitive conclusion to be reached on the role played by aluminium in human neurodegenerative disease.
Aluminium is not a member of the human metallome4. However, its omnipresence in human tissue and especially the brain cannot be without consequence. It is only inimical to life, there is no homeostasis, and it is always a burden to life’s processes. Every atom of aluminium in human brain tissue must be accommodated as aluminium as Al3+(aq), is highly biologically reactive. Life is robust and some aluminium in human brain tissue is tolerated without overt effects. We need to define such limits in the terms of both quantity and location and we need to be more fully aware of human exposure to aluminium. We may then live healthily in the aluminium age (https://www.hippocraticpost.com/mens-health/the-aluminium-age/).
An additional feature which should probably be highlighted is the fact that human beings vary considerably in their sensitivity to aluminum. Nevertheless, aluminum contamination of the environment is preventable/avoidable. The major source of human brain, aluminum toxicity/accumulation, is from atmospheric (stratospheric and tropospheric) nanoparticulate spraying which should be totally banned throughout the world.