| Abstract [eng] |
One of the main causes of dementia development is Alzheimer's disease, with Aβ42 amyloid considered one of its primary pathological agents due to its ability to aggregate and form fibrils. The efficiancy of drugs that inhibit amyloid aggregation depends on the composition of the media used in experimental studies. Accurate replication of physiological conditions can influence the aggregation properties of the Aβ42 amyloid, affecting fibril morphology and aggregation kinetics, and may also affect the interaction between the drug and its targets, thereby positively or negatively impacting its effectiveness. The aim of this study was to evaluate the kinetic and morphological (fibril structure, size, and distribution) properties of the Aβ42 amyloid protein aggregates in artificial cerebrospinal fluid (aCSF) and in the physiological buffer PBS. To achieve this aim, aggregation kinetics of Aβ42 were studied in both aCSF and PBS, with the results indicating that fibrils aggregate faster in PBS. Atomic force microscopy analysis revealed that Aβ42 fibrils in aCSF are more dispersed, taller, and exhibit a broader height distribution compared to fibrils formed in PBS. Additionally, cryo-electron microscopy results showed that Aβ42 fibrils affected by the inhibitor can be morphologically classified into a greater number of classes than those in the control group without the inhibitor. In the samples treated by the inhibitor, thinner fibrils with more twists dominate compared to the control samples without the inhibitor. |
