Lipid matrix plays a role in Abeta fibril kinetics and morphology

Abstract

While neuronal membranes are proposed to be the primary target of amyloid plaques, the effect of phospholipids on fibril formation kinetics and morphology has not yet been resolved. We report that interaction of various compositions with neuronal mimics promoted different processes of fibril formation: negatively charged surfaces increased the lag time and elongation rate in thioflavin T assays, while brain total lipid extract had an opposite effect compared to that in the absence of lipid. Electron microscopy showed thin and elongated fibrils when the peptide was incubated with anionic lipids, while neutral surfaces promoted coarse and small fibrils. Circular dichroism and thioflavin T assays confirmed an initially unstructured peptide, and measured its transition to an aggregated beta-sheet conformation. Structured summary Amyloid beta(1–42) binds to Amyloid beta(1–42) by circular dichroism (View interaction) Amyloid beta(1–42) binds to Amyloid beta(1–42) by fluorescence technology (View interaction) Amyloid beta(1–42) binds to Amyloid beta(1–42) by electron microscopy (View interaction).