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Chronic aluminum intake causes Alzheimer's disease: applying Sir Austin Bradford Hill's causality criteria.
J Alzheimers Dis. 2014; 40(4):765-838.JA

Abstract

Industrialized societies produce many convenience foods with aluminum additives that enhance various food properties and use alum (aluminum sulfate or aluminum potassium sulfate) in water treatment to enable delivery of large volumes of drinking water to millions of urban consumers. The present causality analysis evaluates the extent to which the routine, life-long intake, and metabolism of aluminum compounds can account for Alzheimer's disease (AD), using Austin Bradford Hill's nine epidemiological and experimental causality criteria, including strength of the relationship, consistency, specificity, temporality, dose-dependent response, biological rationale, coherence with existing knowledge, experimental evidence, and analogy. Mechanisms that underlie the risk of low concentrations of aluminum relate to (1) aluminum's absorption rates, allowing the impression that aluminum is safe to ingest and as an additive in food and drinking water treatment, (2) aluminum's slow progressive uptake into the brain over a long prodromal phase, and (3) aluminum's similarity to iron, in terms of ionic size, allows aluminum to use iron-evolved mechanisms to enter the highly-active, iron-dependent cells responsible for memory processing. Aluminum particularly accumulates in these iron-dependent cells to toxic levels, dysregulating iron homeostasis and causing microtubule depletion, eventually producing changes that result in disconnection of neuronal afferents and efferents, loss of function and regional atrophy consistent with MRI findings in AD brains. AD is a human form of chronic aluminum neurotoxicity. The causality analysis demonstrates that chronic aluminum intake causes AD.

Authors+Show Affiliations

Faculty of Medicine, University of New South Wales, St George Hospital, Sydney, Australia.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

24577474

Citation

Walton, J R.. "Chronic Aluminum Intake Causes Alzheimer's Disease: Applying Sir Austin Bradford Hill's Causality Criteria." Journal of Alzheimer's Disease : JAD, vol. 40, no. 4, 2014, pp. 765-838.
Walton JR. Chronic aluminum intake causes Alzheimer's disease: applying Sir Austin Bradford Hill's causality criteria. J Alzheimers Dis. 2014;40(4):765-838.
Walton, J. R. (2014). Chronic aluminum intake causes Alzheimer's disease: applying Sir Austin Bradford Hill's causality criteria. Journal of Alzheimer's Disease : JAD, 40(4), 765-838. https://doi.org/10.3233/JAD-132204
Walton JR. Chronic Aluminum Intake Causes Alzheimer's Disease: Applying Sir Austin Bradford Hill's Causality Criteria. J Alzheimers Dis. 2014;40(4):765-838. PubMed PMID: 24577474.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic aluminum intake causes Alzheimer's disease: applying Sir Austin Bradford Hill's causality criteria. A1 - Walton,J R, PY - 2014/3/1/entrez PY - 2014/3/1/pubmed PY - 2015/1/7/medline KW - Aluminum KW - Alzheimer's disease KW - amyloidogenesis KW - animal disease models KW - causality KW - disconnection KW - entorhinal cortex KW - microtubules KW - neurofibrillary tangles KW - transferrin receptors SP - 765 EP - 838 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 40 IS - 4 N2 - Industrialized societies produce many convenience foods with aluminum additives that enhance various food properties and use alum (aluminum sulfate or aluminum potassium sulfate) in water treatment to enable delivery of large volumes of drinking water to millions of urban consumers. The present causality analysis evaluates the extent to which the routine, life-long intake, and metabolism of aluminum compounds can account for Alzheimer's disease (AD), using Austin Bradford Hill's nine epidemiological and experimental causality criteria, including strength of the relationship, consistency, specificity, temporality, dose-dependent response, biological rationale, coherence with existing knowledge, experimental evidence, and analogy. Mechanisms that underlie the risk of low concentrations of aluminum relate to (1) aluminum's absorption rates, allowing the impression that aluminum is safe to ingest and as an additive in food and drinking water treatment, (2) aluminum's slow progressive uptake into the brain over a long prodromal phase, and (3) aluminum's similarity to iron, in terms of ionic size, allows aluminum to use iron-evolved mechanisms to enter the highly-active, iron-dependent cells responsible for memory processing. Aluminum particularly accumulates in these iron-dependent cells to toxic levels, dysregulating iron homeostasis and causing microtubule depletion, eventually producing changes that result in disconnection of neuronal afferents and efferents, loss of function and regional atrophy consistent with MRI findings in AD brains. AD is a human form of chronic aluminum neurotoxicity. The causality analysis demonstrates that chronic aluminum intake causes AD. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/24577474/Chronic_aluminum_intake_causes_Alzheimer's_disease:_applying_Sir_Austin_Bradford_Hill's_causality_criteria_ DB - PRIME DP - Unbound Medicine ER -