Ical processes of AD start decades before the first symptoms appear, the objective of all AD proteomics studies have been to identify precisely the early diagnostic and prognostic biomarkers. Here we review reports that have used diverse Pevonedistat samples including blood, CSF, brain tissues and also discuss different aspects of proteome status like posttranslational modifications (PTMs), redox proteomics and interaction proteomics. Blood and CSF proteomics studies are being done for more than a decade to identify AD-related biomarkers, of which the most widely researched one is the peptide Amyloid (A). Utility of A as a predictor of dementia and AD is well established and it is evident that lower A42:A40 ratios are mainly associated with the disease [7]. In 2007, a plasma proteomic study in AD patients identified six potential plasma biomarkers using 2D-GE and LC/MS/MS [8]. Some of them, for example -1 antitrypsin, could be validated for its higher expression level in plasma of AD patients using ELISA. Apolipoprotein J was found to be in lower abundance in plasma of AD patients in an isoform-specific manner. This observation could only be achieved through 2-DE but could not be validated through biochemical methods like ELISA or Western blot. Recently, a large scale replication study was conducted for 94 proteins out of 163 potential candidate biomarkers found in 21 published blood proteomics studies. 9 were found to be associated with AD-related phenotypes [9]. It was concluded that there are replicable changes in proteomic expressions in blood of AD patients that can be identified by different studies with some consistency. The rationale of studying plasma and CSF biomarkers for AD has been explicitly reviewed [10] and the diagnostic performance of the core CSF biomarkers, namely total tau, phosphorylated tau and A-42 has been discussed. But studying these traditional biomarkers is not sufficient to identify preclinical AD. Study of differential proteome from whole tissue/body fluids in the disease model compared to that of the normal control is of immense importance in order to identify key, novel protein candidates for the disease. Recently, combination of A, tau and p-tau along with several novel biomarkers in CSF have been used extensively for diagnostic confirmation of AD [11]. It is realized that co-development of biomarkers for early diagnosis and novel therapeutic approaches, together could be the way to go. A recent review has extensively discussed the features of neurodegeneration proteomics and its importance in relation to PTM [12]. Evaluation of functional alterations in proteins due to PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/16989806 PTMs can be achieved by means of a battery of proteomic tools. For the elucidation of pathogenic mechanisms, study of PTMs in AD is of immenseimportance and would become the future of proteomics research to understand the disease process. Very recently, the CSF glycoproteome was studied as a fingerprint of the brain glycoproteome of AD patients [13] and it is concluded that CSF N-glycome analysis may provide reliable biomarkers for early diagnosis of the disease. In many studies, proteins from CSF of AD patients are shown to have differential isoforms in terms of glycosylation [14], S-nitrosylation [15] and histone protein modifications [16] in different tissue sections of the AD brain. Recently quantitative phosphoproteomics studies in the frontal cortex [17] and hippocampi [18] of AD brains have deciphered the deregulation of biological pathways i.