Peripheral anti-A[Beta] antibody alters CNS and plasma A[Beta] clearance and decreases brain A[Beta] burden in a mouse model of Alzheimer's disease

Active immunization with the amyloid [Beta] (A[Beta]) peptide has been shown to decrease brain A[Beta] deposition in transgenic mouse models of Alzheimer's disease and certain peripherally administered anti-A[Beta] antibodies were shown to mimic this effect. In exploring factors that alter A[Beta] metabolism and clearance, we found that a monoclonal antibody (m266) directed against the central domain of A[Beta] was able to bind and completely sequester plasma A[Beta]. Peripheral administration of m266 to PDAPP transgenic mice, in which A[Beta] is generated specifically within the central nervous system (CNS), results in a rapid 1,000-fold increase in plasma A[Beta], due, in part, to a change in A[Beta] equilibrium between the CNS and plasma. Although peripheral administration of m266 to PDAPP mice markedly reduces A[Beta] deposition, m266 did not bind to A[Beta] deposits in the brain. Thus, m266 appears to reduce brain A[Beta] burden by altering CNS and plasma A[Beta] clearance.