Aluminum Neurotoxicity in Neurodegenerative Diseases

Aluminium is a pervasive element in the environment that, despite its abundance, has no known physiological role in human biology. Chronic exposure through diet, water, air and pharmaceuticals can lead to accumulation within the central nervous system, particularly in regions vulnerable to neurodegeneration. Aluminium crosses the blood–brain barrier via transferrin-mediated pathways and can catalyse the generation of reactive oxygen species, disrupt mitochondrial function and promote neuroinflammatory cascades. At the molecular level, aluminium ions can bind to amyloidogenic proteins, facilitating the oligomerisation of β-amyloid and stabilising hyperphosphorylated tau, thereby amplifying the formation of senile plaques and neurofibrillary tangles characteristic of Alzheimer’s disease. In Parkinson’s disease and other movement disorders, aluminium may contribute to dopaminergic neuronal loss by exacerbating mitochondrial dysfunction and α-synuclein aggregation. Epidemiological studies have detected elevated aluminium levels in post-mortem brain tissue from patients with Alzheimer’s disease, multiple sclerosis and autism spectrum disorder. While causality remains debated, mounting experimental evidence supports a role for aluminium as a modulator of neurotoxic pathways. The global significance of aluminium neurotoxicity underscores the need for exposure mitigation strategies, advances in detection within biological tissues and the development of chelation or antioxidant therapies to counteract its deleterious effects.

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Aluminum Neurotoxicity in Neurodegenerative Diseases publication trend

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Technical terms

Blood–brain barrier: A selective physiological barrier composed of endothelial cells that regulates the passage of substances from the bloodstream into the central nervous system.

Oxidative stress: An imbalance between the production of reactive oxygen species and antioxidant defences, leading to cellular damage.

β-Amyloid: Peptides derived from amyloid precursor protein that aggregate to form insoluble plaques in Alzheimer’s disease.

Tau phosphorylation: The chemical addition of phosphate groups to tau protein, which promotes its aggregation into neurofibrillary tangles.

Neuroinflammation: The activation of glial cells and release of inflammatory mediators within the brain, contributing to neuronal injury.

References

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5. Aluminium in human brain tissue from donors without neurodegenerative disease: A comparison with Alzheimer’s disease, multiple sclerosis and autism. Scientific Reports (2020).