Summary
This review examines the long-debated link between aluminum (Al) exposure and Alzheimer’s disease (AD), arguing that aluminum is a plausible and significant contributor to the disease’s development. Although often dismissed on the grounds that bioavailable aluminum cannot reach the brain in harmful quantities, is efficiently excreted, or accumulates only after neurons die, research contradicts each of these assumptions. The authors emphasize that the brain—highly compartmentalized and metabolically vulnerable—requires only very small amounts of aluminum to trigger neurotoxicity, levels easily met through everyday dietary exposure. Aluminum has been shown to hijack multiple transport pathways to cross the blood–brain barrier, accumulate selectively in AD-prone neural regions over a lifetime, and persist due to inefficient clearance. Furthermore, more than a century of experimental evidence demonstrates that chronic aluminum exposure can reproduce the key neuropathological features of AD, including amyloid aggregation, tau pathology, oxidative stress, and neuronal degeneration. Together, these findings challenge long-held misconceptions about aluminum bioavailability and support the hypothesis that Al plays a meaningful, potentially causal role in AD. The authors argue that reducing human aluminum exposure is an urgent and practical step that could mitigate a major, avoidable risk factor for Alzheimer’s disease.
PMID: 21157018
DOI: 10.3233/JAD-2010-101494
Abstract
The brain is a highly compartmentalized organ exceptionally susceptible to accumulation of metabolic errors. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of the elderly and is characterized by regional specificity of neural aberrations associated with higher cognitive functions. Aluminum (Al) is the most abundant neurotoxic metal on earth, widely bioavailable to humans and repeatedly shown to accumulate in AD-susceptible neuronal foci. In spite of this, the role of Al in AD has been heavily disputed based on the following claims: 1) bioavailable Al cannot enter the brain in sufficient amounts to cause damage, 2) excess Al is efficiently excreted from the body, and 3) Al accumulation in neurons is a consequence rather than a cause of neuronal loss. Research, however, reveals that: 1) very small amounts of Al are needed to produce neurotoxicity and this criterion is satisfied through dietary Al intake, 2) Al sequesters different transport mechanisms to actively traverse brain barriers, 3) incremental acquisition of small amounts of Al over a lifetime favors its selective accumulation in brain tissues, and 4) since 1911, experimental evidence has repeatedly demonstrated that chronic Al intoxication reproduces neuropathological hallmarks of AD. Misconceptions about Al bioavailability may have mislead scientists regarding the significance of Al in the pathogenesis of AD. The hypothesis that Al significantly contributes to AD is built upon very solid experimental evidence and should not be dismissed. Immediate steps should be taken to lessen human exposure to Al, which may be the single most aggravating and avoidable factor related to AD.
Tomljenovic L. Aluminum and Alzheimer's disease: after a century of controversy, is there a plausible link? J Alzheimers Dis. 2011;23(4):567-98. doi: 10.3233/JAD-2010-101494. PMID: 21157018.