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 (AD) 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 AD assemblies. Here, we demonstrate the dissociation of AD aggregates using a guided plasma system delivering multimodal stimuli-plasma-induced multi-stimulation (PIMS). PIMS effectively disrupted cross-D sheet-rich AD fibrils through structural alterations mediated by non-enzymatic chemical modifications. The potential of PIMS was further validated by the attenuation of mature AD plaques in brain slices from an AD transgenic mouse model. These findings position PIMS as a potential physicochemical perturbation modality for targeted AD intervention, supporting the development of future disease-modifying strategies for AD.