The present study employs a blend of molecular dynamics simulations and a theoretical model to explore the potential disintegration mechanism of a matured Aβ octamer, aiming to offer a strategy to combat Alzheimer's disease. We investigate local heating and crowding effects on Aβ disintegration by selectively heating key Aβ segments and varying the concentration of sodium dodecyl sulphate (SDS), respectively. Despite initiation of disruption, Aβ aggregates resist complete disintegration during local heating due to rapid thermal energy distribution to the surrounding water. Conversely, although SDS molecules effectively inhibit Aβ aggregation at higher concentration through micelle formation, they fail to completely disintegrate the aggregate due to the exceedingly high energy barrier. To address the sampling challenge posed by the formidable energy barrier, we have performed well-tempered metadynamics simulations. Simulations reveal a multi-step disintegration mechanism for the Aβ octamer, suggesting a probable sequence: octamer → pentamer/hexamer ⇌ tetramer → monomer, with a rate-determining step constituting 45 kJ mol barrier during the octamer to pentamer/hexamer transition. Additionally, we have proposed a novel two-state mean-field model based on Ising spins that offers an insight into the kinetics of the Aβ growth process and external perturbation effects on disintegration. Thus, the current simulation study, coupled with the newly introduced mean-field model, offers an insight into the detailed mechanisms underlying the Aβ aggregation process, guiding potential strategies for effective disintegration of Aβ aggregates.