Developmental Exposure to Metals and its Contribution to Age-Related Neurodegeneration

Experimental and epidemiological evidence suggests that exposure to toxicants during early life can be associated with significantly increased risk of disease later in life, during adulthood and/or aging. The concept of developmental origins of health and disease includes a variety of fetal-early life environmental conditions and numerous adult and age-related diseases, including neurodegenerative diseases. Exposure to certain metals during perinatal development has been shown to elicit long-term changes in the central nervous system that may indicate the presence of neurodegenerative diseases, such as Parkinson's disease or Alzheimer's disease (AD). The neurotoxic metal lead, in particular, has been shown in a series of animal studies in rats, mice, and nonhuman primates, to induce expression of specific markers for AD, such as amyloid beta and hyperphosphorylated tau. Similar, albeit more limited evidence, also exist for arsenic. For both metals, the underlying mechanisms are unknown, but epigenetic changes have been suggested. Follow-up investigations of human cohorts exposed in utero to lead or arsenic would allow verification of such potentially relevant findings.