Mitochondrial Disruption by Amyloid Beta 42 Identified by Proteomics and Pathway Mapping

Alzheimer's disease (AD) is marked by chronic neurodegeneration associated with the occurrence of plaques containing amyloid beta (A beta) proteins in various parts of the human brain. An increase in several A beta fragments is well documented in patients with AD and anti-amyloid targeting is an emerging area of therapy. Soluble A beta can bind to various cell surface and intracellular molecules with the pathogenic A beta(42) fragment leading to neurotoxicity. Here we examined the effect of A beta(42) on network adaptations in the proteome of nerve growth factor (NGF) differentiated PC12 cells using liquid-chromatography electrospray ionization mass spectrometry (LC-ESI MS/MS) proteomics. Whole-cell peptide mass fingerprinting was coupled to bioinformatic gene set enrichment analysis (GSEA) in order to identify differentially represented proteins and related gene ontology (GO) pathways within A beta(42) treated cells. Our results underscore a role for A beta(42) in disrupting proteome responses for signaling, bioenergetics, and morphology in mitochondria. These findings highlight the specific components of the mitochondrial response during A beta(42) neurotoxicity and suggest several new biomarkers for detection and surveillance of amyloid disease.

Automated summary

This study revealed that Aβ(42) disrupts proteome responses for signaling, bioenergetics, and morphology in mitochondria. These findings highlight the specific components of the mitochondrial response during Aβ(42) neurotoxicity and suggest several new biomarkers for detection and surveillance of amyloid disease.