Oxidative stress - Alzheimer's disease - DNA methylation: the role of arsenic

Alzheimer's disease (AD) is a neurodegenerative disease, representing the seventh cause of death worldwide and the first cause of dementia. Several pathogenic mechanisms have been connected to this pathology, including protein aggregation, oxidative stress, metabolic dysfunction, mitochondrial dysfunction, neuroinflammation, synaptic dysfunction, and cell death. The etiology of AD is multifactorial, suggesting that, in addition to a genetic component, the environment may strongly influence its onset and progression. Exposure to heavy metals, such as lead, cadmium, mercury, and arsenic (As), is known to be associated with AD, with As showing one of the strongest correlations, in relation to the epigenetic changes. The World Health Organization (WHO) set a very low limit for its concentration to 10 μg/l in drinking water. The possibility that As may induce epigenetic effects is a recent hypothesis. Evidence, so far, suggests that As may induce DNA hypomethylation in the brain, by mechanisms not yet completely disclosed. This minireview aims to provide evidence to support the role of As exposure in AD, maintaining a focus on oxidative stress and ferroptosis, with a perspective on DNA methylation.