Quantification of N-terminal amyloid-β isoforms reveals isomers are the most abundant form of the amyloid-β peptide in sporadic Alzheimer's disease.

ABSTRACT: Plaques that characterize Alzheimer's disease accumulate over 20 years as a result of decreased clearance of amyloid-β peptides. Such long-lived peptides are subjected to multiple post-translational modifications, in particular isomerization. Using liquid chromatography ion mobility separations mass spectrometry, we characterized the most common isomerized amyloid-β peptides present in the temporal cortex of sporadic Alzheimer's disease brains. Quantitative assessment of amyloid-β N-terminus revealed that > 80% of aspartates (Asp-1 and Asp-7) in the N-terminus was isomerized, making isomerization the most dominant post-translational modification of amyloid-β in Alzheimer's disease brain. Total amyloid-β_1-15 was ∼85% isomerized at Asp-1 and/or Asp-7 residues, with only 15% unmodi

SUBMITTER: Mukherjee S 

PROVIDER: S-EPMC8062259 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature