Post-Translational Modifications Distinguish Amyloid-β Isoforms in Cerebral Amyloid Angiopathy and Alzheimer's Disease.

ABSTRACT: Cerebral amyloid angiopathy (CAA) shares amyloid-β (Aβ) deposition as a pathological hallmark with the extracellular plaques of Alzheimer's disease (AD). While both disease processes involve progressive, decades-long deposition of fibrillar Aβ peptide, they differ in isoform composition. We hypothesized that post-translational modifications (PTMs) on Aβ would also differ between CAA and parenchymal plaques. Using Lys-N enzymatic digestion followed by quantitative mass spectrometry, we profiled Aβ isoforms and N-terminus PTMs (aspartic acid isomerization and pyroglutamate formation) across CAA severity and compared them to parenchymal plaque Aβ in AD. Moderate to severe CAA were dominated by intact N-terminus (Aβ_1-x ~ 95%) with minimal N-truncated species (Aβ_2-x, Aβ

SUBMITTER: Koutarapu S 

PROVIDER: S-EPMC12745913 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature