Identification of post-translational modifications of Aβ peptide in platelet membranes from patients with cerebral amyloid angiopathy

Abstract

Cerebral amyloid angiopathy (CAA) is characterized by cerebrovascular amyloid deposition. It contributes to the rate of cognitive decline in older individuals and is present in >90% of patients with Alzheimer's disease (AD), with no cure so far. Molecular modifications during CAA should be elucidated to improve its diagnosis and treatment. In this study, amyloid-β (Aβ) aggregates in platelet membranes from 65 patients with CAA and 66 healthy volunteers (controls) were confirmed through thioflavin T (ThT) assay and Western blot analysis. Further, post-translational modifications (PTMs) of Aβ in platelet membranes were analyzed using ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC/ESI-Q-TOF/MS). ThT assay results indicated that there were amyloid components in platelets from both patients with CAA and controls. Western blot analysis showed that different molecular weight (MW) Aβ aggregates were found in platelet membranes. LC-MS analysis showed that PTMs including methylation, phosphopantetheine, phosphorylation, deamidation, and acetylation, occurred in Aβ peptide in platelet membranes from both patients with CAA and controls, while Met35 oxidation (MetOX) and Gln15 deamidation were identified only from patients with CAA. Thus, this study identified potential biomarkers of CAA and characterized the mechanism underlying amyloidogenesis in CAA.