Journal article

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

Soumya Mukherjee, Keyla A Perez, Larissa C Lago, Stephan Klatt, Catriona A McLean, Ian E Birchall, Kevin J Barnham, Colin L Masters, Blaine R Roberts

BRAIN COMMUNICATIONS | OXFORD UNIV PRESS | Published : 2021

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. Tot..

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