Biomarkers Of Salivary Exosomes In Patients With Alzheimer's Disease

Alzheimer's disease(AD)is a degenerative neurodegenerative disease of the central nervous system.The typical pathological feature is extracellular senile plaques in the brain caused by ?-amyloid Precipitation and neurofibrillary tangles caused by Tau hyperphosphorylation,as well as massive loss of neurons.AD disease may occur many years before cognitive deficits occur.Mild cognitive impairment(MCI)is an intermediate stage between cognitive normal and dementia.The cognitive function of most MCI patients exists Mild damage,but clinically did not reach the diagnostic criteria for dementia,about 10% to 15% of MCI patients are converted to AD every year.Imaging and scale testing are the main clinical diagnostic methods,but there is no sensitive and non-invasive biomarker diagnostic method.Therefore,it is urgent to find a biomarker for early screening.Exosomes are small vesicles actively secreted by cells and are an important means of communication between cells.Saliva can reflect the whole state of blood and body to a certain extent.The literature on exosome carrying AD-related A?1-42 and Tau protein has been reported,but there is no research on AD salivary exosome proteome.In this paper,AD salivary exosome protein was used as a research object,and the possibility of exosome protein as an AD biomarker was studied by proteomics.First,we established a mass spectrometry-based saliva kit for extracting exosomes and urea buffer to extract exosomal proteins.This method has good reproducibility,low sample dosage,stable detection results,and can be excreted in saliva.Screening for markers of disease in the body provides a methodological reference.Further,we used the mass spectrometry semi-quantitative method and the iTRAQ quantification method to analyze the salivary exosomes of AD,MCI,and CON groups,and initially screened 73 salivary exosome protein biomarkers.Combined with the existing literature reports and the test of 18 AD and 8 CON control samples,we obtained 23 potential biomarkers,which were classified into the following three categories according to their characteristics:(1),low expression in the CON group,There are also low-expression proteins in the AD group : PTX3,ORM1,PRDX3;(2),low expression in the CON group,high expression in the AD group: ITGAM,ITGB2,AZU1,GCA,ELANE,CHI3L1;(3),The CON group had expression,and the AD group had significantly higher expression of the protein compared to the CON group: CAPN1,ANXA3,MPO,MYH9,IQGAP1,MMP9,MYL6,VIM,LTF,ACTN1,ACTN4,S100A12,S100A9,S100A8.