The overarching goal of this study was to test the hypothesis that peripheral administration of antibodies against amyloid beta-peptide would be  sufficient to reduce beta amyloid burden in a mouse model of AD. In summary this study presented evidence that: 1) that passively administered antibodies against Aβ peptide reduced the extent of beta amyloid plaque deposition in the PDAPP mouse model of AD; 2)despite their relatively modest serum levels, the passively administered antibodies were able to enter the central nervous system, decorate plaques and induce clearance of preexisting beta amyloid; 3)antibody entry into the CNS was not due to abnormal leakage of the blood–brain barrier, as there was no increase in vascular permeability in PDAPP mice. In addition, when examined in an ex vivo assay with sections of PDAPP or Alzheimer disease brain tissue, antibodies against amyloid β-peptide triggered microglial cells to clear plaques through Fc receptor-mediated phagocytosis and subsequent peptide degradation. These results indicate that antibodies can cross the blood–brain barrier to act directly in the central nervous system and should be considered as a therapeutic approach for the treatment of Alzheimer disease and other neurological disorders.