Proteomics reveals ribosome associated proteins as potential biomarkers of Alzheimer's disease

Abstract

Abstract Accumulated evidences confirmed that amyloid-β (Aβ) deposition, tau phosphorylation, acetylcholine decrease, etc, all contributed to the pathogenesis of Alzheimer's disease (AD). However, the underlying mechanism remains unclear, and novel AD biomarkers are urgently needed to be discovered. Herein, APP/PS1 double transgenic mice (AD mice) were employed, and the differentially expressed (DE) proteins of mice hippocampus were identified and analyzed by 4D label Free quantitative proteomics technology and parallel reaction monitoring (PRM). The results indicated that the hippocampus of AD mice showed significant Aβ deposition. Compared to that of wild type mice, 29 proteins were up-regulated and 25 proteins were down-regulated in the AD mice group. Gene Ontology (GO) enrichment analysis of BP showed that DE proteins were mainly enriched in Ribosomal large subunit biogenesis. MF results showed that DE proteins were mainly enriched in 5.8S rRNA binding and Structural constituent of ribosome. CC results showed that DE proteins were mainly enriched in Polysomal ribosome, Cytosolic large ribosomal subunit, Cytosolic ribosome, Large ribosomal subunit, etc. KEGG results showed that DE proteins were mainly enriched in the Ribosome signaling pathway. The main target proteins were Rpl18, Rpl17, Rpl19, Rpl24, Rpl35, and Rpl6, which all showed significant differentially expression compared with the wild type mice. The PRM verification results were consistent with the results of 4D Label-free quantitative proteomics. Taken together, our findings revealed that Rpl18, Rpl17, Rpl19, Rpl24, Rpl35 and Rpl6 as AD biomarkers may be the potential targets for drugs design.