The interaction between iron-heme and amyloid-β (Aβ) peptides can be strongly influenced by the cellular compartment. The presence of sodium dodecyl sulfate as a lipid-mimicking system shows a protective role of the membrane by hindering both the formation of the heme–Aβ complex and the peroxidase-like activity, reducing the accessibility of the lipid-bound catalyst to biological substrates, as neurotransmitters.

Alzheimer's disease is an age-related neurodegenerative disorder and the main cause of dementia in the elderly. The accumulation of metal ions, including iron-heme, their interaction with amyloid-β (Aβ) peptides and their ability to catalyze reactive oxygen species formation significantly contribute to the pathogenesis of the disorder. These factors are highly dependent on the surrounding environment, whether intracellular, extracellular, or membrane-associated. In this study, the interaction between heme and Aβ within a membrane-mimicking system using sodium dodecyl sulfate is investigated. UV–vis and circular dichroism data indicate that the heme/Aβ complex can be sequestered within the micelle, leaving part of Aβ largely exposed at the surface. The presence of the micellar environment significantly affects both the stability and aggregation state of the hemin group, as well as its accessibility to peptide coordination and to external molecules, such as phenols and catechols. Indeed, peroxidase-like activity studies show that the overall reactivity of the hemin–Aβ complex is markedly reduced under these conditions. Overall, these results suggest that a membrane-like environment may offer partial neuroprotection against heme-induced toxicity by limiting the formation of the heme–Aβ complex and the oxidative damage to nearby biomolecules, including neurotransmitters.