Bibliographic
Active immunization with the amyloid β (Aβ) peptide has been shown to decrease brain Aβ deposition in transgenic mouse models of Alzheimer's disease and certain peripherally administered anti-Aβ antibodies have been shown to mimic this effect. These results raise questions regarding the mechanism(s) by which anti-Aβ antibodies mediate the clearance of Aβ deposits. One mechanism that has been proposed attributes the anti-amyloid activity of anti-Aβ antibodies to their entry into the CNS followed by local antibody (Fc)-mediated Aβ plaque clearance. This mechanism is was supported by evidence from ex vivo and in vitro experiments in which the presence of added anti-Aβ antibody induced exogenously added microglia-mediated clearance of Aβ deposits in brain slices. In this study the authors provide evidence for another mechanism accounting for the anti-amyloid activity of anti-Aβ antibodies. The authors found that a monoclonal antibody m266 directed against the central domain of Aβ was able to bind and completely sequester plasma Aβ. Peripheral administration of m266 to PDAPP transgenic mice, in which Aβ is generated specifically within the CNS, resulted in a rapid 1,000-fold increase in plasma Aβ, due, in part, to a change in Aβ equilibrium between the CNS and plasma. Although peripheral administration of m266 to PDAPP mice markedly reduced CNS Aβ deposition, m266 did not bind to Aβ deposits in the brain. Based on these data the the authors propose that m266 reduced brain Aβ burden by altering CNS and plasma Aβ clearance. In other words m266 (and other anti-Aβ antibodies) are able to clear Aβ from the CNS of Tg mice, and by extrapolation AD patients, by acting as Aβ sinks.