Beta amyloid (Aβ ) peptide, which is a common neuropathological hallmark deposit in the brain of patients with Alzheimer's disease, typically comprises 39-43 amino acid residues. Aβ peptides exist as isoforms of Aβ 1-40 and Aβ1-42 with various lengths. In this research, atomic force microscopy (AFM) was applied to investigate Aβ 1-40 aggregations in Hank's Balanced Salt Solution. Toxic effect of Aβ1-40 oligomer was investigated in live SH-SY5Y neuroblastoma cells by characterizing cell morphology and cell mechanics using high-resolution AFM scanning. Aβ 1-40 oligomer-induced cytoskeleton reorganization was also observed under confocal microscopy, and it can account for reduction in Young's modulus of cells. Meanwhile, phosphorylation of tau increased after Aβ 1-40 oligomer treatment, possibly resulting inmicrotubule disassembly. This paper demonstrates the linkage between cellular mechanical changes and neurodegeneration mediated by Aβ 1-40. The method used implies promising applications of real-time monitoring of cellular mechanical properties given the toxic effects of Aβ 1-40 on living neuronal cells.