Interference with microtubule stability by beta-amyloid peptide (Ab) has been shown to disrupt dendritic function and axonal trafficking, both early events in Alzheimer's disease. However, it is unclear whether Ab regulation of microtubule dynamics can occur independently of its action on tau. RhoA has been implicated in neurotoxicity by Ab but the mechanism by which this activation generates cytoskeletal changes is also unclear. We found that oligomeric Ab 1-42 induced the formation of stable detyrosinated microtubules in NIH3T3 cells and this function resulted from the activation of a RhoA-dependent microtubule stabilization pathway regulated by integrin signaling and the formin mDia1. Induction of microtubule stability by Ab was also initiated by dimerization of APP and required caspase activity, two previously characterized regulators of neurotoxicity downstream of Ab. Finally, we found that this function was conserved in primary neurons and abolished by Rho inactivation, reinforcing a link between induction of stable detyrosinated microtubules and neuropathogenesis by Ab. Our study reveals a novel activity of Ab on the microtubule cytoskeleton that is independent of tau and associated with pathways linked to microtubule stabilization and Ab-mediated neurotoxicity.