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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Grants

Awarded by National Health and Medical Research Council (NHMRC) Dementia Leadership Fellowship


Awarded by NHMRC project


Funding Acknowledgements

Funding was from National Health and Medical Research Council (NHMRC) Dementia Leadership Fellowship (B.R.R., APP1138673), NHMRC project (B.R.R., APP1164692), and Alzheimer's Drug Discovery Foundation (ADDF).