Table 1.

Roles of different micronutrients in Alzheimer’s disease

Micronutrient	Key findings related to AD
Copper	Plaques of neurofibrillary tangle, amyloid, and soluble oligomers have large amounts of copper at their core[18]
	AD patients have significantly higher levels of copper in brain tissues[19-21]
	Copper promotes neurofibrillary tangle of hyperphosphorylation Tau and oxidative stress[22]
	Copper is useful marker for the diagnostic and prevention of AD[27]
Zinc	Zinc and selenium or iron and zinc have been concomitantly used to treat AD[35,36]
	Combination of zinc and copper accelerates the formation of amorphous aggregates of amyloid protein[40]
	High saturation magnetization of zinc ferrite improves the formation of amorphous aggregates of amyloid protein[41]
	Zinc increases the expression of amyloid precursor protein in a mouse model of AD[43]
	Zinc deficiency leads to a decrease in the learning ability and memory of AD mice[51]
Iron	Markedly increased concentration of ferritin and hemosiderin aggregates in the brain tissues of patients with severe AD[55]
	Iron dysregulation in brain neurons plays a key role in AD[57]
	Iron deposition increases Tau levels in brain tissue and promotes neurofibrillary Tangle Tau formation[10,59]
	Iron accelerates the deposition of amyloid proteins in brain tissues[60]
	Iron oxide nanoparticles have been used in clinical studies to improve AD[68]
Selenium	Chondroitin sulfate selenium improves spatial learning and memory impairment in mice with AD[75]
	The combination of nano-selenium and stem cells increases the levels of brain-derived neurotrophic factor and reduces amyloid deposition in AD mice[77]
	Selenium ameliorates the decrease of cognitive ability[78,79]
Silicon	Silicon may lower the risk of AD[82]
	The unique cross-linking ability of soluble silicic acid and its antagonism to toxic aluminum may protect against AD[83]
Manganese	Excessive intake of manganese can affect the structure and function of astrocytes, as well as the synthesis and degradation of glutamate. Effective control of manganese neurotoxicity may be a potential strategy for preventing or slowing AD[88]
	Abnormal conformation of prion proteins in normal cells can lead to their transformation into pathogenic prion proteins, which can bind to manganese, copper, and zinc, and thus induce AD[89]
	Manganese-rich nanocapsules improve cognitive ability in animal models with AD[93]
Arsenic	Sodium arsenite increases Tau phosphorylation and promotes the formation of neurofibrils in human neuroblastoma cells[94]
	Presence of arsenic in drinking water induces accumulation of amyloid proteins in the frontal cortex and hippocampus of AD mice[95]
	Sodium arsenite causes behavioral disorders and memory change in male AD rats[96]
	The levels of arsenic in the nails and hair of AD patients were higher than that in healthy controls[97]
Vitamin D	Vitamin D regulates innate and adaptive immune responses, which may play a role in the development of AD[98]
	Vitamin D enhances the immune function and may delay aging; thus, it may be used in AD treatment[99]

AD: Alzheimer’s disease.