The accumulation of amyloid beta (Aβ1-42) results in neurotoxicity and is strongly related to neurodegenerative disorders, especially Alzheimer's disease (AD), but the underlying molecular mechanism is still poorly understood. Therefore, there is an urgent need for researchers to discover the proteins that interact with Aβ1-42 to determine the molecular basis. Previously, we developed peptide-ligand-induced changes in the abundance of proTeinS (PACTS)-assisted thermal proteome profiling (TPP) to identify proteins that interact with peptide ligands. In the present study, we applied this technique to analyze clinical samples to identify Aβ1-42-interacting proteins. We detected 115 proteins that interact with Aβ1-42 in human frontal lobe tissue. Pathway enrichment analysis revealed that the differentially expressed proteins were involved mainly in neurodegenerative diseases. Further orthogonal validation revealed that Aβ1-42 interacted with the AD-associated protein mitogen-activated protein kinase 3 (MAPK3), and knockdown of the Aβ1-42 amyloid precursor protein (APP) inhibited the MAPK signaling pathway, suggesting potential functional roles for Aβ1-42 in interacting with MAPK3. Overall, this study demonstrated the application of the PACTS-TPP in clinical samples and provided a valuable data source for research on neurodegenerative diseases.
Keywords: Alzheimer’s disease; amyloid beta 1−42; peptide-ligand-induced abundance change of proteins; thermal proteome profiling.