Metal Toxicity Links to Alzheimer's Disease and Neuroinflammation

Abstract

As the median age of the population increases, the number of individuals with Alzheimer's disease (AD) and the associated socioeconomic burden are predicted to worsen. 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. These environmental risk factors can play a key role in accelerating or decelerating disease onset and progression. 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. 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. 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). 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. Our goal is to increase the awareness of metals as players in the onset and progression of AD.

Agricultural Use of Copper and Its Link to Alzheimer’s Disease

“…Huat et al [ 74 ], in a recent review, stated that “considering the robust evidence for copper’s essential roles in the brain, it is not surprising that many studies have proposed that an imbalance in its homeostasis is associated with neurodegenerative disorders”.…”

Neuropathological Mechanisms Associated with Pesticides in Alzheimer’s Disease

“…Environmental toxicants have been extensively linked to neurodegenerative disorders [24,25]. Homeostatic dysregulation of metals in brain cells and tissues or the accumulation of toxic metals have been linked to various neurodegenerative diseases, including AD [26,27]. Lead (Pb) is known to be neurotoxic and perturbs Aβ generation and clearance [28], and Pb exposure has been implicated in AD [29], but case-control studies have not nailed down a clear link between tissue Pb accumulation and AD [30].…”

Positive association between soil arsenic concentration and mortality from alzheimer’s disease in mainland China

“…As reported in several previous articles, lead, cadmium, and mercury are associated with Alzheimer's disease [19][20][21][22][23]. So we also studied the correlation between the concentration of these metals in the soil and the mortality of Alzheimer's disease (Table 3).…”