Alzheimer's Disease Isomerization

ABSTRACT: Amino acid isomerization is a spontaneous chemical modification potentially related to the underlying causes of Alzheimer’s disease (AD). We demonstrate that data-independent acquisition mass spectrometry can be used to characterize isomerization in complex protein mixtures. Examination of a large cohort of brain samples revealed a striking relationship between isomerization of tau and AD status. Surprisingly, isomerization was found to be more abundant in both autosomal dominant and sporadic AD samples relative to controls. We hypothesize that lower autophagic flux in AD brains accounts for these results. Additional data strongly support this hypothesis, including quantitative analysis of proteins related to autophagy. For example, isomerization of tau is positively correlated with levels of p62, a recognized indicator of autophagic inhibition. In sum, the data suggest strong ties between isomerization and autophagic flux, which may therefore represent a promising target for future investigations into the therapy and prevention of AD.

ORGANISM(S): Homo Sapiens

SUBMITTER: Gennifer Merrihew  

PROVIDER: PXD025668 | panorama | Wed Mar 16 00:00:00 GMT 2022

REPOSITORIES: PanoramaPublic