Amyloid-Beta Peptide Aβ3pE-42 Induces Lipid Peroxidation, Membrane Permeabilization and Calcium-Influx in Neurons

Abstract

Pyroglutamate-modified amyloid- (pΕ-Aβ) is a highly neurotoxic amyloid-β (Aβ) isoform and is enriched in the brains of individuals with Alzheimer disease compared with healthy aged controls. Pyroglutamate formation increases the rate ofAβ oligomerization and alters the interactions of Aβ with Cu2+ and lipids; however, a link between these properties and the toxicity of pE-Aβ peptides has not been established.Wereport here that Aβ3pE-42 has an enhanced capacity to cause lipid peroxidation in primary cortical mouse neurons compared with the fulllength isoform (Aβ(1-42)). In contrast, Aβ(1-42) caused a significant elevation in cytosolic reactive oxygen species, whereas Aβ3pE-42 did not.Wealso r..