Alzheimer’s disease (AD) is a neurodegenerative disease mainly caused by the accumulation of β-amyloid (Aβ) monomer molecules, leading to the formation of senile plaque, intracellular neurofibrillary tangles, and memory loss in the elderly. Recent evidences suggest that oligomeric Aβ species are a major risk factor in the progress of AD. In this study, we prepared Aβ oligomer and cross-linked Aβ oligomer to beaded-polyacrylamide resin. Aβ oligomer specific polyclonal antibodies (Ab-Aβo) were isolated from IVIG by Aβ oligomer affinity chromatography and their characteristics were identified by ELISA and Western blot assay. The effect of Ab-Aβo on cytotoxicity was further analyzed by MTT assay. The results showed that purified Ab-Aβo specifically recognized both synthesized and cell-produced Aβ oligomers. Compared with IVIG, the binding activity of the antibodies to Aβ oligomers was increased by 1000 times and Ab-Aβo significantly attenuated Aβ42-induced cytotoxicity in SH-SY5Y neuroblastoma cells, suggesting that Ab-Aβo may be a potential immunotherapeutic for the treatment of AD.