Inactivation of seeding activity of amyloid β-protein aggregates in vitro

The deposition of amyloid beta-protein (A beta) in the brain is a major pathological feature of Alzheimer's disease (AD). Recent studies have reported that A beta pathology can be transmitted among individuals through medical procedures in humans, as well as animal models, and the prevention of A beta pathology transmission is of great importance to public health. To assess the effect of autoclaving (AC) or gamma (gamma)-ray irradiation on A beta pathology transmission, we evaluated the seeding effect of A beta aggregates using thioflavin T (ThT) assays and high-speed atomic force microscopy (HS-AFM) and investigated the structural changes in the A beta aggregates after treatment with AC or gamma-ray irradiation using ThT assays, circular dichroism (CD) spectroscopy, and electron microscopy (EM). The ThT assays and HS-AFM showed that the seeding effect of A beta aggregates was inactivated by AC at different temperatures, exposure times, and concentrations of A beta aggregates during treatment with AC. The results of the ThT fluorescence and CD spectral patterns of the autoclaved A beta aggregates indicate that AC reduced beta-sheet-rich structures in A beta aggregates. The EM images demonstrated that the length of the autoclaved A beta aggregates with fibril-like structures was significantly shorter than that of the untreated ones. Gamma-ray irradiation of A beta aggregates did not lead to significant inactivation of the A beta seeding effect or cause structural changes in A beta aggregates. In conclusion, autoclaving A beta aggregates decreases beta-sheet-rich structures and reduces A beta seeding activity, which could lead to the development of effective methods for preventing the propagation of A beta pathology among individuals.