Influence of Zeolites on Amyloid-β Aggregation

Aggregation of Aβ plays a key role in the progression of Alzheimer's disease. Unfortunately, the Aβ aggregation mechanism is complex, leading to a structurally diverse population of oligomers and amyloid fibrils. Heterogeneous interfaces have been shown to influence the rate of fibrilization and may be useful tools to bias amyloid formation toward specific structures. In order to better understand how exogenous materials influence Aβ aggregation, Aβ_1-40 was exposed to zeolite Y containing different metal cations, including Na⁺, Mg²⁺, Fe³⁺, Zn²⁺, and Cu²⁺. NaY, MgY, and FeY, all accelerated the kinetics of fibrilization by increasing the primary nucleation rate, while CuY and ZnY inhibited fibrilization. These kinetic effects were supported through binding affinity measurements, in which ZnY and CuY showed higher association constants than the other zeolites. In addition to influencing the kinetics of fibrilization, the zeolites also affected the intermediate structures along the pathway. Western blots confirmed that Aβ_1-40 was arrested at the oligomeric stage in the presence of ZnY and CuY, while continuing to the fibrillary state in the presence of other zeolites. Seeding studies showed that NaY and FeY form on-pathway oligomers, while ZnY formed off-pathway oligomers. Overall, our results show that zeolites can impact the aggregation and speciation of amyloids.