Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer's disease model

This study investigated effects of passive immunization on brain Aβ levels and cognitive deficits in old PDAPP Tg mice. Previous studies have shown that chronic treatment with the monoclonal antibody m266, specific for Aβ, increases plasma concentrations of Aβ and reduces Aβ burden in young PDAPP Tg mice. This study reports that administration of m266 to 24 month old PDAPP mice can rapidly reverse memory deficits in both an object recognition task and a holeboard learning and memory task, but without altering brain Aβ burden. Results also found that an Aβ/antibody complex was present in both the plasma and the cerebrospinal fluid of m266- treated mice. This data indicates that passive immunization with this anti-Aβ monoclonal antibody can very rapidly reverse memory impairment in certain learning and memory tasks in the PDAPP mouse model of AD, owing perhaps to enhanced peripheral clearance and (or) sequestration of a soluble brain Aβ species.