Our century is an “aluminium age”; Aluminum is used in many areas of our daily lives, such as vaccine aids, antacids, food additives, skin care products, cosmetics and cookware, and can occur as elements or contaminants found in many foods, including infant formula, dairy products, juice, wine, seafood and tea. From the nineteenth century, aluminum was found and extracted from rocks, and because of its excellent chemical and physical properties, such as low gravity, ductility, malleability, reflectivity, high tensile strength, corrosion resistance, easy to be machined into shapes and high electrical conductivity, it was quickly used in incredible amounts used for many purposes; we have entered an 'aluminium age'. Bauxite is a kind of aluminum salt and the main raw material that needs to be refined to produce alumina, from which aluminum metal is recovered by electrolytic reduction; aluminum is also recycled from scrap metal.
Exposure of Aluminum by Human Being
Dietary Aluminum Exposure
- Aluminum in Tea and Cookwares
- Aluminum Exposure from Infant Milk and Formula
- Aluminum in Other Foods
- Aluminum in Drinking Water
If an adult eats 327.10 g of youtiao per week, which is quite possible in China, the weekly dietary intake of aluminum would exceed the PTWI [50]. Therefore, most of the aluminum in dairy products should be contaminants during processing, depending on the complexity of the processing technology.
Aluminum Exposure by Medication and Personal Care Products
Aluminum Exposure by Occupation
Occupational exposure to aluminum occurs in industries in the form of McIntyre powder, aluminum oxide, aluminum sulfate, aluminum dust and fumes in pot rooms, and aluminum fumes during welding of aluminum sheets during the production of automobiles, airplanes, trains, and ships. According to the studies, the concentrations of aluminum dust or vapor in the air of workplaces vary from 0 to several tens of mg/.
Aluminum Bioavailability and Influencing Factors
Some Important Influencing Factors on Oral Aluminum Absorption
Fluoride Fluoride appears to increase aluminum absorption; the mechanism may be the formation of multiple complexes with aluminum. Some dietary compounds, such as phytate and polyphenols, can chemically bind to aluminum and affect aluminum absorption [73, 74].
![Fig. 1.4Aluminum concentrations in brain tissues of different ages. (Quoted from Ref. [56])](https://thumb-ap.123doks.com/thumbv2/azdoknet/10594331.0/19.659.146.570.130.846/fig-4aluminum-concentrations-brain-tissues-different-ages-quoted.webp)
Adverse Effect of Aluminum on Human Being
- Neurotoxic Effects Induced by Occupational Aluminum Exposure
- Aluminum Exposure in Drinking Water and Neurological Disorders
- Antacids Ingestion and Development of AD
- Aluminum-Related ALS and PDT in Specific Regions
- Aluminum and Neurodevelopmental Toxicity
However, the cause of potroom asthma has been suggested to be the exposure to fluorides in the workplace air [48]. In the initial report of the study, the OR for impaired cognitive function was 1.14 (not significant) for median Al concentration (>0.085 mg/l) in drinking water compared to lower Al concentrations.
Conclusions
Flaten TP (1990) Geographical associations between aluminum in drinking water and mortality rates with dementia (including Alzheimer's disease), Parkinson's disease and amyotrophic lateral sclerosis in Norway. Martyn CN, Barker DJ, Osmond C, Harris EC, Edwardson JA, Lacey RF (1989) Geographic association between Alzheimer's disease and aluminum in drinking water.
The Chemistry of Human Exposure to Aluminium
The equilibria governing the distribution of aqueous aluminum monomers (Eq. 2.1) are practically instantaneous. However, the toxicity of aluminum adjuvants is not necessarily limited to the delivery of Al3+(aq) at the injection site.
Entry and Deposit of Aluminum in the Brain
Aluminum Enters into the Brain
- Aluminum Enters into the Brain Across BBB
- Aluminum Influxes into the Brain Across BBB Directly as a Small Molecular Weight Pieces
- Aluminum Entry into the Brain Is Mediated by Transferrin (Tf)-Transferrin Receptor (TfR), Which Is an Important Iron
- Aluminum Citrate Enters into the Brain Mediated
- Aluminum Citrate Enters into the Brain via System Xc–, Which Is Known to Be a Na + -Independent Glutamate Transporter,
- Aluminum-Containing Compounds Could Enter into the Brain Through the Olfactory Mucosa/Olfactory Bulb
- Little Aluminum Enters the Brain Through Choroid Plexus
Cells in the brain possess a specific high-affinity receptor for Tf that is independent of the metal being transported. System xc activity is very important for maintaining the intracellular glutathione level and the redox balance between cystine and cysteine in the extracellular environment [22].
Aluminum Effluxes from the Brain
There is little opportunity for the choroid plexus and CSF compartment than through rapid exchange between blood and the brain through the BBB aluminum citrate was administered via the femoral vein. So aluminum primarily enters the brain from blood through the BBB rather than through the choroid plexus, and some aluminum enters the brain through the choroid plexus.
The Influence Factors of Aluminum Entry and Deposition in the Brain
- Parathyroid Hormone (PTH) and Vitamin D
- Permeability of the BBB
- Citric Acid
Some compounds of aluminum can injure BBB, whereby increasing the permeability of the blood-brain barrier can promote the entry of aluminum into the brain. Banks WA, Kastin AJ (1989) Aluminum-induced neurotoxicity: changes in membrane function at the blood-brain barrier.
Aluminum as a CNS and Immune System Toxin Across the Life Span
Introduction: Neurological Diseases and Causality Factors
- Aluminum Toxicity: General Considerations for the Impact on Human Neurological Diseases
At the same time, studies of any of the above-mentioned sporadic neurological diseases have failed to detect a single environmental factor (see details and references in Shaw [122]), although such has been clearly demonstrated in several unrelated neurological diseases. clusters, such as those involving methylmercury poisoning or lathyrism (see Shaw [122]). An emerging view, although not necessarily unified, is that most age-related neurological diseases at any given time in life probably result from some complex interplay of genetic susceptibility factors (of which there may be several) and toxic exposures in each individual exposure factor ( many more than one such factor) that may be relatively unique to each affected individual (for additional references see Shaw [122]).
Aluminum in the Biosphere and Forms of Human Exposure
- Aluminum Chemistry and the Intersection of Aluminum with the Biosphere
- Sources of Aluminum in the Biosphere
- Aluminum in Vaccines
It is also apparently not an "essential" element, as some medical websites (eg, Children's Hospital of Philadelphia [22]) have erroneously claimed. Regarding CNS levels, the amount of aluminum in the normal adult human brain is less than 2 μg/g [3], with a distribution reflecting higher concentrations in gray compared to white matter [18].
![Table 4.1 highlights some of the key sources of bioavailable aluminum to which humans are exposed (excerpted from Tomljenovic [139]](https://thumb-ap.123doks.com/thumbv2/azdoknet/10594331.0/62.659.80.588.110.500/table-highlights-sources-bioavailable-aluminum-exposed-excerpted-tomljenovic.webp)
Human and Animal Studies of Aluminum Neurotoxicity
- Aluminum-Triggered Genetic Alterations and Protein Expression Levels
- miRNA Alterations in Gene Expression
Histological examination revealed inflammatory lesions in the brain and spinal cord associated with the presence of aluminum. Such modification does not require or generally involve any changes in the DNA sequence itself. It reduces expression of the neuron-specific neurofilament light chain (NFL) gene in 86% of surviving neurons in the superior temporal gyrus of AD patients.
Overview of Innate Versus Adaptive Immune Systems and Their Roles in CNS Development and Neurological
- HPA–Immune System Interactions in Development and Disease
- Autoimmunity
- Aluminum and Failed Biosemiosis
- Aluminum’s Role in Immune System Signaling Errors with a Focus on ASD
- Pathogen and Aluminum Activation of the Immune System in Relation to the CNS
Abnormalities in the amygdala [62, 97] and changes in cortisol levels indicative of a dysfunctional HPA axis are common in children with ASD and may serve, in part, to explain these children's limited abilities to respond adequately to their social environment. as well as their tendency towards enhanced anxiety behaviors [59, 113]. Thus, as mentioned above, the impact of aluminum on the CNS is likely to be a component of bidirectional aspects of CNS-immune system interactions. In this context, persistent CNS inflammation appears to play an important role in neurodevelopmental and neurodegenerative disorders.
Summary and Final Considerations
Blaylock RL, Strunecka A (2009) Immune-glutamatergic dysfunction as a central mechanism of autism spectrum disorders. Petrilli V, Papin S, Dostert C, Mayor A, Martinon F, Tschopp J (2007) Activation of the NALP3 inflammasome is induced by low intracellular potassium concentration. Purcell AE, Jeon OH, Zimmerman AW, Blue ME, Pevsner J (2001) Postmortem brain abnormalities of the glutamate neurotransmitter system in autism.
Occupational Exposure to Aluminum and Cognitive Impairment
- Introduction
- Exposure Assessment
- Cognitive Impairment
- Conclusion
Al concentration in urine in the exposed group was 24 μg/gCr, and in the control group 4.7 μg/gCr. In the first study, the concentration of Al in the plasma of exposed workers was 8.7 μg/l, while that of controls was 4.3 μg/l. In another study, the concentration of Al in the plasma of exposed workers was 6.7 μg/l, while that of controls was 4.3 μg/l.
Exposure to Aluminum in Daily Life and Alzheimer’s Disease
- Introduction
- Natural Sources of Aluminum Exposure
- Anthropogenic Sources of Aluminum Exposure
- Aluminum Exposures of General Population in Daily Life
- Absorption, Distribution, and Excretion of Aluminum
- Aluminum-Induced Neurotoxicity and Aluminum Hypothesis in Etiology of AD
- Aluminum and A β
- Aluminum and NFTs
- Aluminum and Cell Death
- Epidemiological Evidence of a Relation
Aluminum is also released due to anthropogenic activities such as mining and industrial use, in the production of aluminum metal and other aluminum compounds [6]. With increasing accumulation of aluminum in the brain, an increased burden of amyloid plaques was also observed in patients with renal failure. Al induces apoptosis in the astrocytes, which further leads to neuronal death by loss of the neurotrophic support [27].
Between Aluminum Intake in Daily Life and Alzheimer’s Disease
Conclusions
Bhattacharjee S, Zhao Y, Hill JM, Percy ME, Lukiw WJ (2014) Aluminum and its possible contribution to Alzheimer's disease (AD). Walton JR (2010) Evidence for the involvement of aluminum in neurofibrillary tangle formation and growth in Alzheimer's disease. Walton JR, Wang MX (2009) APP expression, distribution, and accumulation are altered by aluminum in a rodent model of Alzheimer's disease.
Animal Model of Aluminum-Induced Alzheimer’s Disease
- The Involvement of Aluminum in AD
- The Aluminum Compounds for Animal Model .1 The Complex Chemistry of Aluminum
- The Aluminum Salts and Complexes
- The Aged Rabbits Are More Effective as Animal Model
- The Susceptibility of Aged Rabbits in Inducing AD Neuropathology Compared to Young Ones
- The Al-Induced Neurodegeneration
- The Similar Features in Al-Maltolate-Treated Rabbits with AD Patients
- Neurofibrillary Degeneration
- Oxidative Stress
- Apoptosis
- Summary
NFTs, oxidative stress damage and apoptosis were observed in the hippocampus of aged rabbits treated with Al maltolate. But these pathological changes are not found in the hippocampus of young rabbits treated with Al-maltolate. Brain regions are less affected in the case of young rabbits treated with Al-maltolate compared to old ones [27-29].
Aluminum-Induced Neural Cell Death
Introduction
First, we demonstrate Al-induced cell death in neuron, neuroglia cells, and co-cultured neural cells separately to illustrate the neurotoxic effects. Second, we test the modes of Al-induced cell death using signaling pathway inhibitors. In vivo experiments are significant for Al neurotoxicity research; this may provide an underlined mechanism in Al-induced neural cell death and further give potential therapeutic strategies to neurodegenerative diseases.
Aluminum-Induced Neural Cell Death
- Methods
- Results
- Cellular Morphology in Al-Treated Neural Cells
- Nuclei Morphology in Al-Treated Neural Cells
- Apoptosis Detection by TUNEL
- Ultrastructure of Al-Treated Neurons
- Cell Death Rates Detected by Flow Cytometry
- Discussion
However, in Al-treated glial cells there were no typical morphological changes in the nuclei (bI-bIV). In Al-treated co-cultured neural cells, a few hypercondensed chromatins and shrunken nuclei were observed (cl-cIV). There were significant increases in necrotic rates and total cell death rates for Al-treated astrocytes (b).
Necroptosis in Aluminum-Induced Neural Cell Death
- Methods
- Results
- Morphology and Cell Viability of SH-SY5Y Cells Treated with Al and Nec-1
- Apoptotic Rate and Necrotic Rate Assay
- Caspase Activity of Al- and Nec-1-Treated SH-SY5Y Cells
- LC3 Expression of Al- and Nec-1-Treated SH-SY5Y Cells
- Discussion
Cell viability was consistent with the morphology of the cells treated with 0-8 mM Al and Nec-1 (60 μM) and is presented in Table 8.1. To test the role of Nec-1 on MMP and ROS, the 4 mM Al-treated cells were infused with Nec-1 (Table 8.6). LC3 expression of the cells treated with 0–8 mM Al increased significantly (p < 0.05) as shown in Fig.
Al-Induced Neural Cell Loss and AD
- Methods
- Results
- Cell Viability Analysis In Vitro
- Fluorescent Observation and Analysis on Neural Cell Death Rates In Vitro
- Western Blot Analysis on Expression of Cell Death-Related Proteins In Vitro
- Neural Behavioral Profile in Mice
- Nec-1 Decreased Neural Cell Death Induced by Al In Vivo
- Expression of Cell Death-Related Proteins in Cortical Neural Cells In Vivo
- Expression of AD-Related Proteins in Mice
- Discussion
Morphology of neural cells treated with 2 mM Al and 2 mM Al plus 60 M Nec1 was examined by fluorescent microscope (A-I), and cell death rates were quantified by cytometry (J). The cells treated with 2 mM Al plus 60 μM Nec-1 (c) showed reduction of necrotic cells (f) and apoptotic cells (i). Western blot data demonstrated the inhibition of cell death-related proteins in cortical neural cells exposed to 2 mM Al plus 2–8 mM Nec-1.
Conclusions
Wang Z, Wei X, Yang J, Suo J, Chen J, Liu X et al (2016) Chronic exposure to aluminum and risk of Alzheimer's disease: a meta-analysis. Gupta VB, Anitha S, Hegde ML, Zecca L, Garruto RM, Ravid R et al (2005) Aluminum in Alzheimer's disease: are we still at a crossroads. Savory J, Herman MM, Ghribi O (2006) Mechanisms of aluminum-induced neurodegeneration in animals: implications for Alzheimer's disease.
Aluminum-Induced Electrophysiological Variation, Synaptic Plasticity Impairment,
Aluminum Neurotoxicity
The possible role of aluminum in the etiology of neurodegenerative diseases, such as Alzheimer's dementia since 1973 [4]. Moreover, the neurotoxic effects of Al on mouse neurobehavioral profiles were confirmed [7] and neurotoxic symptoms were observed, showing that Al also impairs neurobehavioral function. Studies in animal models and cell cultures have revealed that Al exposure results in altered behavioral performance and memory impairment.
Al-Induced Electrophysiological Variation
- Aluminum Effect on Electrical Excitability
- Aluminum Effect on Voltage-Operated Ion Channels
- Aluminum Effect on Synaptic Plasticity
- The Cell Signal Pathways and Aluminum Effect on Synaptic Plasticity
- Glutamate-NO-cGMP and Aluminum Effect on Synaptic Plasticity
- PLC Signaling Pathway and Aluminum Effect on Synaptic Plasticity
- Ca 2+ -CaM-CaMKII Signaling Pathway and Aluminum Effect on Synaptic Plasticity
- The MAPK Pathway and Aluminum Effect on Synaptic Plasticity There are four subtypes of MAPK, namely, extracellular signal-regulated protein
- Wnt Pathway and Aluminum Effect on Synaptic Plasticity
Recent studies have also shown that the activation of several signaling pathways in the hippocampus of rats plays a key role in long-term memory. The Ca2+-CaM-CaMKII signaling pathway in the rat hippocampus plays a key role in long-term memory. Wang [42] found that aluminum inhibits CaMKII expression in rat brain and Ca2+-CaM-CaMKII signal transduction.
Conclusion and Future Perspectives
Platt B et al (1995) Aluminum impairs long-term potentiation of the hippocampus in rats in vitro and in vivo. Liang RF et al (2012) Aluminum maltolate-induced impairment of learning, memory and long-term potentiation of the hippocampus in rats. Song J et al (2014) Effects of aluminum exposure on long-term potentiation and AMPA receptor subunits in rats in vivo.
Cross Talk Between Aluminum and Genetic Susceptibility and Epigenetic Modification
- Introduction
- Aluminum and AD
- Al and Genetic Susceptibility in AD
- Al and Epigenetic Modification in AD
- Al and Genetic Susceptibility and Epigenetic Modification in AD
- Summary
DNA methylation in the promoter region of a gene has been associated with reduced transcriptional activity. Manivannan Y, Manivannan B, Beach TG, Halden RU (2015) Role of environmental pollutants in the etiology of Alzheimer's disease: a review. Genome-wide12 DNA methylation profiles in the superior temporal gyrus reveal epigenetic signatures associated with Alzheimer's disease.
