Amyloid β Proteoforms Elucidated by Quantitative LC/MS in the 5xFAD Mouse Model of Alzheimer's Disease.

ABSTRACT: Numerous Aβ proteoforms, identified in the human brain, possess differential neurotoxic and aggregation propensities. These proteoforms contribute in unknown ways to the conformations and resultant pathogenicity of oligomers, protofibrils, and fibrils in Alzheimer's disease (AD) manifestation owing to the lack of molecular-level specificity to the exact chemical composition of underlying protein products with widespread interrogating techniques, like immunoassays. We evaluated Aβ proteoform flux using quantitative top-down mass spectrometry (TDMS) in a well-studied 5xFAD mouse model of age-dependent Aβ-amyloidosis. Though the brain-derived Aβ proteoform landscape is largely occupied by Aβ1-42, 25 different forms of Aβ with differential solubility were identified. These proteoforms fall int

SUBMITTER: Kandi S 

PROVIDER: S-EPMC10840081 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature