Early-life Pb exposure as a potential risk factor for Alzheimer's disease: are there hazards for the Mexican population?

Alzheimer's disease (AD) is the main cause of dementia in elderly. Increasing life expectancy is behind the growing prevalence of AD worldwide with approximately 45 million cases currently documented and projection studies suggesting a triplication of this number by 2050. Mexico does not have an accurate AD registry, but 860,000 cases were reported in 2014 and the prediction reaches 3.5 million cases by 2050. Amyloid plaques and neurofibrillary tangles represent the main hallmarks of AD, being constituted of amyloid beta (A beta) peptide and phosphorylated tau, respectively. The risk factors for AD include genetic mutations, lifestyle and environmental pollution. Particularly, lead (Pb) has attracted attention due to its ability to target multiple pathways involved in the pathophysiology of AD. Although the epidemiological data are limiting, animal and in vitro studies show growing evidence of causal effects of Pb exposure on AD-linked features including A beta aggregation and tau phosphorylation. Interestingly, many Pb effects occur selectively following early-life exposure to the metal, suggesting an epigenetic mechanism. This hypothesis is supported by changes in DNA methylation and microRNA expression patterns inflicted by early-life Pb exposure. Pb pollution in Mexico represents a significant problem because past and current mining activities, historical use of Pb as fuel additive and culturally rooted use of Pb in glazed ceramics, contribute to high levels of Pb pollution in Mexico. In this review we will discuss potential risks of AD development in Mexican populations chronically exposed to Pb in their childhood.