Discovery of dehydroamino acids and their crosslinks in Alzheimer's Disease

ABSTRACT: Alzheimer’s disease is characterized by the accumulation of protein aggregates. Dehydroamino acids are rarely observed posttranslational modifications that contain an electrophilic alkene capable of forming protein-protein crosslinks, which may lead to protein aggregation. We used mass spectrometry-based proteomics to discover 412 sites of dehydroamino acid formation in 184 proteins from protein aggregate-enriched human brain samples, an order of magnitude more than observed in the soluble protein fractions. We further report 11 dehydroamino acid-mediated crosslinks, including 3 in the Tau protein that are 10-fold more abundant in Alzheimer’s disease samples compared to age-matched controls. Dehydroamino acids are prevalent modifications in the Alzheimer’s disease brain proteome and give rise to protein crosslinks that may contribute to protein aggregation.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

DISEASE(S): Alzheimer's Disease

SUBMITTER: Samuel Markovich  

LAB HEAD: Lloyd M

PROVIDER: PXD053814 | Pride | 2025-03-06

REPOSITORIES: Pride