Gradual micronutrient accumulation and depletion in Alzheimer's disease

Cadmium is a carcinogen that accumulates relentlessly with age, reaching high levels in the liver and kidneys. It is known to hyperactivate the Kupffer cells (hepatic macrophages). On the other hand, the risk of developing Alzheimer's disease increases considerably with age and it involves neuronal damage by hyperactive microglia (brain macrophages). Moreover, many of the metals that accumulate in the liver and kidneys, also accumulate in the brain (Fe, Cu, Zn, Mn, etc.). Therefore, it is possible that Cd also hyperactivates the microglia, playing a role in Alzheimer's disease (AD).Fe also accumulates in the brain as we age and catalyzes super oxide (O2-) formation, which reacts with nitric oxide (NO) to form the very harmful peroxynitrite (ONOO-). ONOO- causes considerable damage that exacerbates the damage caused by the hyperactive microglia, accelerating the progress of AD. Moreover, as we age we become less efficient at absorbing and retaining Cu, Zn and Mg. Since Cu and Zn are necessary for the synthesis of copper-zinc superoxide dismutase (CuZnSOD), which disables the noxious O2-, the deficiencies cause considerable damage as we age. Similarly, Mg is a cofactor for CuZnSOD and is necessary for NO to leave the cell and perform its vasodilating job. Unfortunately, a Mg deficiency traps the NO in the cell, where it reacts with O2-, forming the harmful ONOO-. Furthermore, Se and vitamins B6 and D are required for Mg absorption and vitamin E is required to minimize the oxidative damage.