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

作者：Ronald Bradley Demattos, Kelly R. Bales, David J. Cummins, Jean‐Cosme Dodart, Steven M. Paul, David M. Holtzman · 发表于：Proceedings of the National Academy of Sciences · 年份：2001 · DOI：10.1073/pnas.151261398 · 被引用次数：1305 · 研究领域：Alzheimer's disease research and treatments、Computational Drug Discovery Methods、Prion Diseases and Protein Misfolding

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.