Analysis Of Peptidome Profiling Of Serum From Patients With Alzheimer Disease

Objective:Alzheimer’s disease(AD) is the most common cause of dementia and is characterized by accumulation of extracellular plaques and intraneuronal neurofibrillary tangles in specific brain region. Despite the many clinical trials conducted, currently no appoved disease-modifying treatment exists. The global societal economic cost of dementia is an enormous sum. Early detection of AD is crucial to evaluate and implement eary intervention strategies and to improve the quality of the individual experience of living with dementia. The aim of this study is to indentify and validate peptidome change in the serum from AD patients and to offer a new way for prevention and treatment of AD.Methods:We collected 25 serum samples from AD patients, and 25 health control(HC) subjects. Hospitalized patients were diagnosed with 24 hours receiving MRI scan and other related auxiliar examination after being admitted to hospital. In detail, moring urine samples were collected and immediately frozen and stored at-80℃. Peptides were enriched and captured by magnetic La PO4–graphene oxide composites(La GM) beads.LC MS/MS analysis was performed with a Triple TOF 5600 System(AB SCIEX, Concord, ON) fitted with a Nanospray III source(AB SCIEX,Concord, ON). The MS/MS data were analyzed for protein identification using Protein Pilot Software v.4.5(AB Sciex Inc.,USA). The local false discovery rate was estimated with the integrated PSPEP tool in the Protein Pilot Software to be 1.0% after searching against Human proteome set database, which contains 175312 protein sequences downloaded from http://www.uniprot.org/uniprot/Results:It showed that Fibrinogen alpha chain、Fibrinogen beta chain、Thymosin beta-4 and ITIH4 were found to exist in whole serum sample.Notably, a combinaion of four peptides(Alpha-2-macroglobulin、Histone、Actin, cytoplasmic 2) show sensitivity and specificity of 80% for discriminating the AD group from the HD group. This combination might be useful for diagnosis of ADConclusion:Serum peptide profile would provide useful AD biomarker candidate,which may have a theragnostic value.