Aluminium and Alzheimer’s Disease: A Suspicious Link (original) (raw)
Related papers
Aluminium in Alzheimer’s disease: are we still at a crossroad
Experientia, 2005
Aluminium, an environmentally abundant non-redox trivalent cation has long been implicated in the pathogenesis of Alzheimer’s disease (AD). However, the definite mechanism of aluminium toxicity in AD is not known. Evidence suggests that trace metal homeostasis plays a crucial role in the normal functioning of the brain, and any disturbance in it can exacerbate events associated with AD. The present paper reviews the scientific literature linking aluminium with AD. The focus is on aluminium levels in brain, region-specific and subcellular distribution, its relation to neurofibrillary tangles, amyloid beta, and other metals. A detailed mechanism of the role of aluminium in oxidative stress and cell death is highlighted. The importance of complex speciation chemistry of aluminium in relation to biology has been emphasized. The debatable role of aluminium in AD and the cross-talk between aluminium and genetic susceptibility are also discussed. Finally, it is concluded based on extensive literature that the neurotoxic effects of aluminium are beyond any doubt, and aluminium as a factor in AD cannot be discarded. However, whether aluminium is a sole factor in AD and whether it is a factor in all AD cases still needs to be understood.
Molecular toxicity of aluminium in relation to neurodegeneration
The Indian journal of medical research, 2008
Exposure to high levels of aluminium (Al) leads to neurofibrillary degeneration and that Al concentration is increased in degenerating neurons in Alzheimer's disease (AD). Nevertheless, the role of Al in AD remains controversial and there is little proof directly interlinking Al to AD. The major problem in understanding Al toxicity is the complex Al speciation chemistry in biological systems. A new dimension is provided to show that Al-maltolate treated aged rabbits can be used as a suitable animal model for understanding the pathology in AD. The intracisternal injection of Al-maltolate into aged New Zealand white rabbits results in pathology that mimics several of the neuropathological, biochemical and behavioural changes as observed in AD. The neurodegenerative effects include the formation of intraneuronal neurofilamentous aggregates that are tau positive, oxidative stress and apoptosis. The present review discusses the role of Al and use of Al-treated aged rabbit as a suitab...
Multifaceted effects of aluminium in neurodegenerative diseases: A review
Biomedicine & Pharmacotherapy, 2016
Aluminium (Al) is the most common metal and widely distributed in our environment. Al was first isolated as an element in 1827, and its use began only after 1886. Al is widely used for industrial applications and consumer products. Apart from these it is also used in cooking utensils and in pharmacological agents, including antacids and antiperspirants from which the element usually enters into the human body. Evidence for the neurotoxicity of Al is described in various studies, but still the exact mechanism of Al toxicity is not known. However, the evidence suggests that the Al can potentiate oxidative stress and inflammatory events and finally leads to cell death. Al is considered as a well-established neurotoxin and have a link between the exposure and development of neurodegenerative diseases, including Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease (AD), dementia, Gulf war syndrome and Parkinsonism. Here, we review the detailed possible pathogenesis of Al neurotoxicity. This review summarizes Al induced events likewise oxidative stress, cell mediated toxicity, apoptosis, inflammatory events in the brain, glutamate toxicity, effects on calcium homeostasis, gene expression and Al induced Neurofibrillary tangle (NFT) formation. Apart from these we also discussed animal models that are commonly used for Al induced neurotoxicity and neurodegeneration studies. These models help to find out a better way to treat and prevent the progression in Al induced neurodegenerative diseases.
Aluminum and Alzheimer's disease: a new look
Journal of Alzheimer's disease : JAD, 2006
Despite the circumstantial and sometimes equivocal support, the hypothetic involvement of aluminum (Al) in the etiology and pathogenesis of Alzheimer's disease (AD) has subsisted in neuroscience. There are very few other examples of scientific hypotheses on the pathogenesis of a disease that have been revisited so many times, once a new method that would allow a test of Al's accumulations in the brain of AD patients or a comparison between Al-induced and AD neuropathological signs has become available. Although objects of methodological controversies for scientists and oversimplification for lay spectators, several lines of evidence have strongly supported the involvement of Al as a secondary aggravating factor or risk factor in the pathogenesis of AD. We review evidence on the similarities and dissimilarities between Al-induced neurofibrillary degeneration and paired helical filaments from AD, the accumulation of Al in neurofibrillary tangles and senile plaques from AD, the...
Brazilian Journal of Pharmaceutical Sciences
Over the years, a handful of drugs have been approved to be used in the fight against Alzheimer's Disease but unfortunately none of these drugs have proven to be solid-treatments. Alzheimer's Disease is one of the most prominent diseases observed in the elderly population. In this review article, we discuss how aluminum toxicity can lead to neuro degeneration. Aluminum is abundantly present on the earth's crust and hence becomes easily accessible to man. This makes it an obvious choice in the preparation of numerous substances, packaging, etc. Such wide usage of the metal can pave an easy access to the body, leading to toxicities. Aluminum toxicity has been linked to oxidative stress which has an established relation with neurodegeneration and mitochondrial damage. We also discuss how consumption of antioxidants can be useful in combating oxidative stress.
Neurotoxicology, 2016
Aluminum (Al) is a very common component of the earth's mineral composition. It is not essential element for life and is a constituent of rather inert minerals. Therefore, it has often been regarded as not presenting a significant health hazard. As a result, aluminum-containing agents been used in the preparation of many foodstuffs processing steps and also in elimination of particulate organic matter from water. More recently, the reduced pH of bodies of water resulting from acid rain has led to mobilization of aluminum-containing minerals into a more soluble form, and these have thus entered residential drinking water resources. By this means, the body burden of aluminum in humans has increased. Epidemiological and experimental findings indicate that aluminum is not as harmless as was previously thought, and that aluminum may contribute to the inception and advancement of Alzheimer's disease. Epidemiological data is reinforced by indications that aluminum exposure can resu...
Aluminum and Neurodegenerative Diseases
Elsevier eBooks, 2017
Aluminum (Al) is a common element found in large amounts in the earth's crust (Priest et al., 1988). Aluminum-containing minerals are present in relatively inert rock types, especially in igneous formations, such as granite and quartz. Laterization of various silicate rocks weathering into finer particles results in the formation of sedimentary bauxite, where together with iron, Al is present largely as the oxide. It is as bauxite that Al is generally mined and second only to iron, Al is the most widely used metal (Hetherington, 2007). Despite its commonality, Al has no known beneficial biological roles and is not an essential element for any organism. Aluminum-containing minerals are rather unreactive, and this is also true for metallic aluminum, as this is quickly oxidized in air and thus coated by a very thin but robust layer of the oxide. This apparent inertness has led to the concept that aluminum may not constitute a health hazard. Consequently a wide range of Al compounds have been added as stabilizers in many processed foods. Alum, which is any trivalent Al-containing salt, is the oldest and most commonly used vaccine adjuvant. Recent findings indicate that the effectiveness of the adjuvant relies on both its immunomodulatory as well as inflammatory properties. Al salts have also found utility in water clarifying processes by effecting precipitation of organic particulate matter. Growing incidence of acidic rain has led to greater solubilization of aluminum salts from their insoluble form in rocks. This has led to an elevated Al content in many water reserves used for residential supply. Thus, human exposure to more soluble forms of Al in water and foodstuffs has grown. Reports from both biological laboratories and from study of human population health indicate that prolonged aluminum ingestion can result in neurological abnormality. Accumulating indications strongly suggest that Al can further the onset and development of neurodegenerative disorders, principally Alzheimer's disease (AD). There are many reports suggesting that Al can provoke excessive inflammatory events in the brain. Superfluous immune reactivity that is not an obvious response to a trauma such as injury or infection is a distinguishing feature of the elderly brain and appears exacerbated in nervous system abnormalities. Most neurodegenerative diseases have no obvious cause and do not have a clear genetic basis. Thus, it is probable that the origin of such diseases lies in unknown environmental influences that interact with the progression of aging. The nature of most of such factors is unknown, but there is growing evidence, indicating that Al is likely to be one of these environmental factors. In this review, reports that point to the conclusion that aluminum are able to speed up the worsening of brain function with age, and potential mechanisms are discussed. It should be noted that acceleration of this process would inevitably increase the prevalence of those specific neurological disorders where age is a concomitant risk factor. 2 Growing Bioavailability of Aluminum in the Environment Metallic aluminum was first made by Hans Oersted in 1825 by heating aluminum chloride with elemental potassium (Sigel and Sigel, 1988). Al-containing chemicals have many uses. Mixing aluminum sulfate and lime together in water leads to formation of colloidal aluminum hydroxide, and this can bring about precipitation and removal of waterborne organic material. This method for water clarification is widely used. Al-containing additives are also found in many foodstuffs. They are used as emulsifying agents in preparation of processed cheese, as crisping agents in pickles, in baking powder, and in a variety of food colorings. Aluminum-containing compounds are also found in cosmetics. Commercial preparations of infant formula can contain significant amounts of the metal (Burrell and Exley, 2010; Dabeka et al., 2011). High concentrations of soluble Al can be found in the juice resulting from boiling of acidic fruit in aluminum cookware (Fimreite et al., 1997). The aluminum content of city water supplies is variable, but on occasion, concentrations as high as 0.4-1 mg/L have been reported in drinking water. Although the health effects of these levels of the metal on humans are uncertain, the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives in 2007 recommended a maximum intake of Al less than 1 mg/kg body weight per week. This corresponds to 63 mg per week for a 140-pound adult. Some commercial pastry products contain Al
Aluminium exposure induces Alzheimer's disease-like histopathological alterations in mouse brain
Histology and histopathology, 2008
Aluminium (Al) is a neurotoxic metal and Al exposure may be a factor in the aetiology of various neurodegenerative diseases such as Alzheimer's disease (AD). The major pathohistological findings in the AD brain are the presence of neuritic plaques containing beta-amyloid (Abeta) which may interfere with neuronal communication. Moreover, it has been observed that GRP78, a stress-response protein induced by conditions that adversely affect endoplasmic reticulum (ER) function, is reduced in the brain of AD patients. In this study, we investigated the correlation between the expression of Abeta and GRP78 in the brain cortex of mice chronically treated with aluminium sulphate. Chronic exposure over 12 months to aluminium sulphate in drinking water resulted in deposition of Abeta similar to that seen in congophilic amyloid angiopathy (CAA) in humans and a reduction in neuronal expression of GRP78 similar to what has previously been observed in Alzheimer's disease. So, we hypothesi...
Neurotoxicity of Aluminium: A Comprehensive Review
International Journal of Biology, Pharmacy and Allied Sciences, 2020
Aluminium is one of the major environmental neurotoxin, whose exposure produces several adverse effects. The severity of damage depends on the time and levels of exposure, the rate of absorption, individual susceptibility and the route by which the metal is absorbed. Aluminium has been reported that it can lead to Alzheimer's disease despite the controversy around the issue. When aluminum is absorbed into your brain, it lasts over a very long period and the half-life is reported to be 20% of lifetime. Although the precise cause of aluminium toxicity is unclear, the studies indicate that aluminium can enhance the inflammatory and oxidative events resulting in the synthesis of reactive oxygen-species and the degradation of antioxidant defense enzymes, which contribute to increased mitochondrial oxidative stress. This review attempts to describe the causes of exposure, symptoms of toxicity and molecular mechanisms by which neurotoxins can cause neurotoxicity, prevention and treatment for the aluminium induced neurotoxicity.