AbstractBackgroundAmyloid fibril formation is associated with protein‐misfolding disorders and is a key pathway for the pathogenesis of Alzheimer’s disease (AD). The fibrillar structure of amyloid beta‐protein (Aβ) is the hallmark of amyloid plaques in the brains of patients with Alzheimer’s disease (AD). The interaction between the cell membrane and the Aβ40 peptide may induce membrane disruption and membrane leakage and may be related to the toxicity in Alzheimer’s disease (AD).MethodIn this regard, we evaluated the competitive effects of different polyelectrolytes such as chitosan (CHT), N‐trimethyl chitosan (TMC), heparin and dextran on peptide‐phospholipid membrane interactions and Aβ40 fibrillation. The impact of polyelectrolytes on AB aggregation at membrane interface and fibrillation of Aβ40 peptide was evaluated by utilizing biophysical techniques such as ThT binding assays and atomic force microscopy.ResultThe polyelectrolytes and lipid membranes co‐exist extensively in the cellular environment, we demonstrate that the interactions of polyelectrolytes and Aβ may substantially influence the role of the N‐terminal charged region of Aβ in initiating and guiding adsorption and aggregation of the peptide on the membrane surface.ConclusionHence, there is a great deal of interest in polyelectrolytes that can bind to the Aβ40 peptide and interfere with the Aβ40 peptide‐membrane interactions and manipulate amyloid formation in Alzheimer’s disease (AD).