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      Is aluminum exposure a risk factor for neurological disorders?

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          Abstract

          Aluminum (Al) is widely found in the nature. Although the relation between Al and neurodegenerative diseases is still controversial, Al is related with many brain diseases including Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Al exposure occurs mainly through environment, occupational, and dietary factors for humans. Al exposure with diet can be through foods, food additives, water, and contamination of Al equipment/utensils. The aim of this review is to summarize various hypotheses, which link Al and neurodegeneration, and to determine the roles of Al exposure through different sources including diet, environment, and occupation. Future studies should be done in vulnerable subgroups of population including children, patients receiving antacid or Al-containing pharmeteucials on a daily basis, patients with reduced renal function, and patients on parenteral nutrition regimens that are likely to be affected by possible adverse health effects of Al. In addition, gender, age, and Al interactions need to be determined. One of the most important challanges in future epidemiological studies is to determine which variables should be controlled. In addition, experimental studies should be more focused and translational. In this context, exposure dose, dose–response effects, and time lapse between exposures and cognitive assessments are very important.

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          Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases

          Neurodegenerative diseases including Alzheimer (AD) and Parkinson (PD) have attracted attention in last decades due to their high incidence worldwide. The etiology of these diseases is still unclear; however the role of the environment as a putative risk factor has gained importance. More worryingly is the evidence that pre- and post-natal exposures to environmental factors predispose to the onset of neurodegenerative diseases in later life. Neurotoxic metals such as lead, mercury, aluminum, cadmium and arsenic, as well as some pesticides and metal-based nanoparticles have been involved in AD due to their ability to increase beta-amyloid (Aβ) peptide and the phosphorylation of Tau protein (P-Tau), causing senile/amyloid plaques and neurofibrillary tangles (NFTs) characteristic of AD. The exposure to lead, manganese, solvents and some pesticides has been related to hallmarks of PD such as mitochondrial dysfunction, alterations in metal homeostasis and aggregation of proteins such as α-synuclein (α-syn), which is a key constituent of Lewy bodies (LB), a crucial factor in PD pathogenesis. Common mechanisms of environmental pollutants to increase Aβ, P-Tau, α-syn and neuronal death have been reported, including the oxidative stress mainly involved in the increase of Aβ and α-syn, and the reduced activity/protein levels of Aβ degrading enzyme (IDE)s such as neprilysin or insulin IDE. In addition, epigenetic mechanisms by maternal nutrient supplementation and exposure to heavy metals and pesticides have been proposed to lead phenotypic diversity and susceptibility to neurodegenerative diseases. This review discusses data from epidemiological and experimental studies about the role of environmental factors in the development of idiopathic AD and PD, and their mechanisms of action.
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            Human health risk assessment for aluminium, aluminium oxide, and aluminium hydroxide.

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              Aluminium as a risk factor in Alzheimer's disease, with emphasis on drinking water.

              Aluminium (Al) is clearly a powerful neurotoxicant. Considerable evidence exists that Al may play a role in the aetiology or pathogenesis of Alzheimer's disease (AD), but whether the link is causal is still open to debate. This paper reviews the epidemiological evidence linking Al and AD. Nine out of 13 published epidemiological studies of Al in drinking water and AD have shown statistically significant positive relations. Given the difficulty in producing high-quality data for the occurrence of AD and also for Al exposure, with the resulting unavoidable misclassification errors biasing any true association towards the null value, these studies are remarkably consistent. A major problem in their interpretation is that drinking water, even at high Al concentrations, only contributes a fraction of the total dietary intake of Al. In particular, regular consumers of antacids ingest gram amounts of Al daily, thousands of times the amounts taken in through drinking water, and epidemiological studies of antacid exposure and AD have been largely negative. However, Al is very poorly absorbed in the gastrointestinal tract, and the possibility that some Al fractions present in drinking water may be particularly bioavailable cannot be dismissed at present. The combined evidence linking Al and AD warrants substantial research efforts. Such efforts should focus on clarification of the cellular and molecular mechanisms in Al toxicity and of the basic metabolism and kinetics of Al in the human body, and on further epidemiological studies including diverse routes of Al exposure and also variables that are known or suspected to influence the individuals' susceptibility to AD, such as apolipoprotein E allele status and family history of AD.
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                Author and article information

                Journal
                J Res Med Sci
                J Res Med Sci
                JRMS
                Journal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences
                Medknow Publications & Media Pvt Ltd (India )
                1735-1995
                1735-7136
                2018
                06 June 2018
                : 23
                : 51
                Affiliations
                [1]Department of Nutrition and Dietetics, Faculty of Health Sciences, Hacettepe University, Ankara, Turkey
                Author notes
                Address for correspondence: Dr. Aylin Ayaz, Department of Nutrition and Dietetics, Faculty of Health Sciences, Hacettepe University, Ankara 06100, Turkey. E-mail: baylin@ 123456hacettepe.edu.tr
                Article
                JRMS-23-51
                10.4103/jrms.JRMS_921_17
                6040147
                30057635
                b307fc8e-f23a-46e4-90eb-2ddb223e013d
                Copyright: © 2018 Journal of Research in Medical Sciences

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                : 04 October 2017
                : 06 February 2018
                : 05 March 2018
                Categories
                Review Article

                Medicine
                aluminum,alzheimer's disease,multiple sclerosis,neurodegenerative diseases,parkinson's disease

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