Amyloid-beta Citrullination in Alzheimer's Disease

ABSTRACT: Amyloid-beta peptides which aggregate and accumulate in Alzheimer’s disease (AD) brain are known to have sequential N-terminal truncations and multiple post-translational modifications (PTM) such as isomerization, pyroglutamate formation, phosphorylation, nitration and dityrosine cross-linking. Here we add to the list of PTM citrullination (deimination) of Arg5 residue in plaque-derived Abeta in sporadic AD brains, identified by tandem mass spectrometry. We quantitated the level of citrullination on multiple N-truncated Abeta isoforms present in plaque-associated fractions and found that almost 30 % of pyroGlu3-Abeta pool was citrullinated in plaques from AD temporal cortex. We also documented citrullinated Abeta peptides in the detergent insoluble fractions from AD frontal cortex with ~ 22 % citrullination in the pyroGlu3-Abeta pool. Citrullination of Abeta is a common PTM, closely associated with pyroglutamate-Abeta formation and Abeta accumulation in AD. This may have implications for Abeta toxicity, auto-antigenicity of Abeta, and may be relevant for the design of diagnostic assays and therapeutic targeting.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

DISEASE(S): Alzheimer's Disease

SUBMITTER: Soumya Mukherjee  

LAB HEAD: Soumya Mukherjee

PROVIDER: PXD025620 | Pride | 2021-11-24

REPOSITORIES: Pride