Negatively Charged Gold Nanoparticles Inhibit Alzheimer's Amyloid-β Fibrillization, Induce Fibril Dissociation, and Mitigate Neurotoxicity

Amyloids are pathogenic hallmarks in many neurodegenerative diseases such as amyloid-beta (A beta) fibrils in Alzheimer's disease (AD). Here, the effect of gold nanoparticles (AuNPs) on amyloids is examined using A beta as a model system. It is found that bare AuNPs inhibited A beta fibrillization to form fragmented fibrils and spherical oligomers. Adding bare AuNPs to preformed A beta fibrils results in ragged species where AuNPs bind preferentially to fibrils. Similar results are demonstrated with carboxyl- but not amine-conjugated AuNPs. Co-incubation of negatively charged AuNPs with A beta relieved A beta toxicity to neuroblastoma. Overall, it is demonstrated that AuNPs possessing negative surface potential serve as nano-chaperones to inhibit and redirect A beta fibrillization, which could contribute to applications for AD.