A Study On The Mechanism Of Alzheimer’s Disease Caused By Aluminum Accumulation In Brain Based On Al³⁺ Promoting Aβ Aggregation

Alzheimer’s Disease（AD）,commonly known as Alzheimer’s disease,is a degenerative disease of the central nervous system,which is extremely common in the elderly population,and its prevention and treatment is one of the world’s problems.Recent advances in the mechanism of the interaction of aluminum and beta-amyloid peptides（amyloid-beta,Aβ）require a re-examination of the relationship between aluminum accumulation in the brain and AD.AD is characterized by the extracellular Aβaggregation in the brain parenchymal tissues and on the cerebral vascular walls,the abnormal phosphorylation of tau protein in neurons and selective loss of synapses in neurons.The excessive deposition of Aβpeptides can form senile plaques（SP）and the abnormal phosphorylation of tau protein can lead to the production of neurofibrillary tangles（NFTs）,causing neurodegenerative changes.These variations result in the decline of human consciousness and the loss of memory,and the occurrence of pathological features such as dementia.Aluminum accumulation in the brain promotes the conversion of Aβfrom monomer to oligomer,which possibly aggravate the aggregation of Aβand leads to the development of Alzheimer’s disease.Then,it is necessary to test how the combined action of AlCl₃ and Aβaffects the migration ability,phagocytic ability and free intracellular Ca²⁺level in microglial cells.The Aβtreatment on nerve cells will cause the damage,Tau protein hyperphosphorylation and lead to the neurofibrillary tangles of neurons,whether Al³⁺will aggravate the damage of Aβto neurons?Both of these are the key scientific problem to be solved in the experiment.This study will provide new ideas for AD prevention and drug design.In this study,a series of experiments of AlCl₃ and Aβtreatments on neurons and microglial cells were performed.Aβwas applied on neuronal cell PC12 to establish a damage neuronal model,and different concentrations of AlCl₃ were added for the experiment.It was shown that AlCl₃ under the concentration of 100μM increases cell livability,and reduces the degree of apoptosis,reactive oxygen species,intracellular calcium ion level and tau phosphorylation level of Aβtreated neuronal cells.And these mean that AlCl₃ below 100μM has protective effect on PC12 cells.AlCl₃ at the concentration above 100μM reduces cell livability,and increases the degree of apoptosis,reactive oxygen species,intracellular calcium ion level,and tau protein phosphorylation level of Aβtreated neuronal cells.And it could be concluded that AlCl₃ above 100μM will aggravate the damage of Aβto PC12 cells.All of the above results showed that the control of aluminum concentration in neurons is crucial for AD.These researches lay a foundation for further researches on the relationship of of aluminum and AD.At the same time,AlCl₃ and Aβwere applied to microglail BV2 cells seperately.It was shown that after the treatments all of the migration ability,phagocytic ability and intracellular free Ca²⁺ion level of the treated microglial cells are increased with the increase of concentrations.BV2 cells were also co-treated by AlCl₃ and Aβtogether,and it was found that the migration,phagocytosis and intracellular free Ca²⁺levels of the cells increased slightly with the increasing of AlCl₃ concentration.After the treatments the releasement of NO,TNF-α、IL-1βand other inflammatory factors were also slightly increased.It can be deduced that AlCl₃ may promote the extracellular calcium influx and the releasing of calcium ions from the endoplasmic reticulum store,which enhance the migration and phagocytic capacity of microglial cells,but the increasing of inflammatory factors will harm the cells in brain.Through the above experimental studies,the following conclusions could be obtained:AlCl₃ at a concentration below 100μM can protect neuronal cells by reducing the Aβaggregation and tau protein phosphorylation in the cells,and AlCl₃ at a concentration above 100μM will exacerbate the Aβaggregation,the phosphorylation of tau protein,elevate the level of reactive oxygen species,and calcium ions in neurons,and may exacerbate the damage of Aβto neurons.AlCl₃increases the intracellular free calcium levels of microglial cells,and the elevated free calcium level further increases the migration and phagocytosis of microglial cells.Over-activation of microglial cells can produce inflammatory factors that damage neurons and aggravate AD.