Role of micronutrients in Alzheimer's disease: Review of available evidence

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.