Aβ1-42 , which is highly toxic to neural cells, is commonly present in the brains of people with Alzheimer's disease. In this study, dynamic changes in cell mechanics were monitored under Aβ-induced toxicity. To investigate the changes in cellular mechanical properties, we used Aβ1-42 oligomer at different concentrations to treat human neuroblastoma SH-SY5H cells. Results demonstrated a two-stage dynamic change in cell mechanics during neurodegeneration. Additionally, Young's modulus (YM) of the treated cells increased in a short period. The reasons include alteration in surface tension, osmotic pressure, and actin polymerization. Rough cellular membranes were observed from atomic force microscope (AFM) measurement. However, the cellular YM gradually decreased when the cells were continuously exposed to Aβ1-42 or to a high concentration of Aβ1-42 . The major reason for the decreased YM was microtubule disassembly. Dynamic change in YM reflects different activities in cytoplasm in response to Aβ1-42 . The characteristic changes in cell mechanics provided insights into the dynamic neurodegeneration process of cells induced by Aβ1-42 oligomer. Copyright © 2019 Published by Elsevier Ltd.