Effect Of A?3-10-kLH Polypeptide Vaccine On Tau Protein Phosphorylation In Tau/APP/PS1 Transgenic Mice

Objective: The main features of Alzheimer's disease are extracellular A?(?-amyloid)plaques(senile plaques,SP),the formation of highly phosphorylated tau proteins(Neurofibrillary Tangles,NFTs)in neurofilament entangled cells and central cholinergic Loss of neurons.Its main clinical manifestations are progressive dementia,cognitive dysfunction,mental and behavioral abnormalities,and decreased ability to live.Although scholars hold different views on the etiology of Alzheimer's disease,the A? hypothesis is still dominant.As people's life expectancy increases,the number of patients suffering from Alzheimer's disease increases,both in developed and developing countries.At present,there is no cure for this disease.Clinically,it can only be treated symptomatically.Therefore,it is of great significance to further study the drugs against Alzheimer's disease.Recent studies have shown that there is an interaction between A? and Tau protein,and the imbalance of the production and elimination of ?-amyloid protein may be the initial event that leads to the degeneration of neurons and the occurrence of cognitive dysfunction.A? deposition can promote the abnormal phosphorylation of Tau protein,while over-phosphorylated Tau protein can exacerbate the effects of A?-induced neuron toxicity and microtubule loss,thereby damaging nerve cells and causing cognitive impairment and learning behavior impairment.At present,studies on the relationship and role of A? deposition and Tau protein phosphorylation in AD are increasing and in-depth,and it is of great significance for the occurrence,progression and prognosis of AD.We established tau/APP/PS1 triple transgenic mice at various time points between deposition of A? until the deposition of A? plaques and cognitive impairment,and explored the prevention of A? deposition in the brain of tau/APP/PS1 mice.Protein phosphorylation,the effect of neuronal fiber tangles.Methods: We constructed the A?3-10-KLH polypeptide vaccine and injected subcutaneous 3 × Tg AD mice in tau / APP / PS1(3×Tg AD)mice as experimental group and C57/B6 wild type mice as control Wild control group,3×Tg AD mice were injected with PBS as a model control group.The first immunization was mixed with an equal volume of Freund's adjuvant(FCA)and injected subcutaneously in the back.The second immunization begins with an equal volume of Freund's Adjuvantin Complete(FIA),which is fully emulsified and injected subcutaneously in the back.The first and second intervals of two weeks,followed monthly,a total of seven times.After the end of immunization,the brain was decapitated,then the content of total tau protein in the brain was detected by ELISA,and the phosphorylation of tau in the brain neurons was detected by western-blot.Results: 1,After 7 immunizations,the level of anti-A? antibody in A?3-10-KLH group was significantly higher than that in PBS group(P <0.05).2,The results of ELISA showed that the total tau protein in the brain of A?3-10-KLH group was significantly decreased compared with the model control group,the difference was statistically significant(P <0.05).3,Western-blot results showed that phosphorylation of tau protein at Ser202/Thr205 and Thr231 sites were significantly reduced in 3×Tg AD mice treated with A?3-10-KLH polypeptide vaccine compared with model mice,The difference was statistically significant(P <0.05).Conclusion: The above results show that in the early stage of AD pathology in 3 × Tg AD mice,the total tau protein in the brain was significantly decreased after multiple injections of the A?3-10-KLH vaccine,and the tau protein was found at Ser202/Thr205 and Thr231 sites phosphorylation was significantly reduced.