In Alzheimer disease, β-amyloid peptide accumulates in the brain as insoluble amyloid plaques. Amyloid filaments, similar to those found in amyloid plaques, can be assembled in vitro from chemically synthesized β-peptides. In this study, we report that antibodies raised against the N-terminal region (1–28) of the β-amyloid peptide bind to the in vitro-formed β-amyloid assemblies, leading to disaggregation of the fibrils and partial restoration of the peptide’s solubility. The concomitant addition of fibrillar β-amyloid with these antibodies to PC 12 cells leads to the inhibition of the neurotoxic effects of β-amyloid. Some of the mAbs raised against soluble β-peptide (1–28) have been found to prevent in vitro fibrillar aggregation of β-amyloid peptide. These experimental data suggest that site-directed mAbs interfere with the aggregation of β-amyloid and trigger reversal to its nontoxic, normal components. The above findings give hints on how to convert in vivo senile plaques into nontoxic, diffuse components and may have therapeutic interest for those studying Alzheimer disease and other human diseases related to amyloidogenic properties of physiological peptides and proteins.