| Alzheimer's disease is a neurodegenerative disease,which also called senile dementia.The most characteristic pathologic hallmarks of AD are neuritic plaques,neurofibrillary tangles and cerebral amyloid angiopathy.Abnormal increase or accumulation of amyloid protein in brain tissue is the main cause of neuronal death.AD pathogenesis is complex,and a variety of factors contribute to it,such as amyloid beta abnormal deposition,Tau protein hyperphosphorylation,oxidative stress,inflammatory response and apoptosis,etc.The pathogenesis of AD experienced before symptoms of AD,mild cognitive impairment and gradually developed into AD.At present,in view of the complexity of AD pathology,there is no clear,specific and reliable laboratory diagnostic methods,it is difficult to carry out early clinical diagnosis,and also affected the treatment of AD,it is particularly important to find biological diagnosis of early Alzheimer's disease biomarkers from the body fluids(such as saliva,blood and urine).Saliva is one of the important sources of body fluid biomarkers,with advantages of easy to collect and deal with.Bioactive molecules in the body can enter saliva through active transportion,passive transportion,or extracellular ultrafiltration.Therefore,similar to blood,the composition of saliva is also related to the physiological and pathological state of the human body,and their components are correlated.For example,about 30% of the blood protein is also present in saliva,and about 20% of the total salivary protein is found in the plasma.Based on the endogenous peptides and low molecular weight proteins,peptidomics study aims at reseaching the composition,function,regulation and their connection.In this paper,we tried to find biomarkers for early diagnosis of AD by means of salivary proteomics.Based on nano liquid chromatography-high resolution tandem mass spectrometry,we analyzed the sequences of salivary peptides,their attributable proteins and their post-translational modifications.First of all,We studied the effect of frozen storage conditions on the composition of salivary peptidome in healthy individuals.The difference in the number of peptides,the similarities and differences between the proteins,their attributable proteins showed that the preservation of saliva samples was better at-80?.Secondly,we examined that the salivary peptidome of samples were affected by different time of the day,the results of MALDI-TOF MS showed that the five sampling time had little effect on salivary peptidome.Finally,based on the results of the previous study,we tried to find the candidate biomarkers from the AD group,the MCI group and the control group,which by comparing the difference of methionine oxidation and the specific proteins in saliva differential peptides.The detected peptides of those selected proteins can be divided into four classes,the proeins related to epigenetic regulation and component of amyloid plaques,like Histone H2 A,Histone H3.2,Histone H1.3,Histone H3.1t,Histone H1.4 etc,the proteins take part in inflammation,such as the Protein S100-A8,Protein S100-A9,Protein S100-A12;correlation of energy metabolism,cytoskeleton and nervous system development,which includes 6-phosphogluconate dehydrogenase?Pyruvate kinase isozymes M1/M2?Phosphoglycerate kinase1,Phosphoglycerate mutase1,Actin,Cofilin-1,Heterogeneous nuclear ribonucleoprotein and so on.In addition,we also in other 15 AD patients,15 MCI patients,8 older controls verified the biomarkers.Our research uesd the method saliva peptidomics compared with the control group and health,and then elaborated the similarities and differences in protein level of salivary peptides,and screened AD salivary peptides potential biomarkers,this method can provide reference for early diagnosis of AD. |
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