![]() We also discuss studies that validate the disruption of immune-related pathways as an important mechanism of toxicity by which metals can contribute to AD. Herein, we review how these metals affect brain physiology and immunity, as well as their roles in the accumulation of toxic AD proteinaceous species (i.e., β-amyloid and tau). As a result, we are exposed not only to essential metals, such as iron, copper, zinc and manganese, but also to toxic metals including lead, aluminum, and cadmium, which perturb metal homeostasis at the cellular and organismal levels. Among known environmental risk factors, chronic exposure to various metals has become more common among the public as the aggressive pace of anthropogenic activities releases excess amount of metals into the environment. These environmental risk factors can play a key role in accelerating or decelerating disease onset and progression. While aging and inherent genetic predisposition play major roles in the onset of AD, lifestyle, physical fitness, medical condition, and social environment have emerged as relevant disease modifiers. As the median age of the population increases, the number of individuals with Alzheimer's disease (AD) and the associated socio-economic burden are predicted to worsen.
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