Plasma-driven disassembly of amyloid-β aggregates by the interplay of physicochemical stimuli

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the aggregation of beta-amyloid (Aβ) peptides and their extracellular deposition in the brain. Atmospheric-pressure plasma, a low-temperature physicochemical modality with growing biomedical interest, offers a promising approach to destabilize Aβ assemblies. Here, we demonstrate the dissociation of Aβ aggregates using a guided plasma system delivering multimodal stimuli—plasma-induced multi-stimulation (PIMS). PIMS effectively disrupted cross-β sheet-rich Aβ fibrils through structural alterations mediated by non-enzymatic chemical modifications. The potential of PIMS was further validated by the attenuation of mature Aβ plaques in brain slices from an AD transgenic mouse model. These findings position PIMS as a potential physicochemical perturbation modality for targeted Aβ intervention, supporting the development of future disease-modifying strategies for AD.