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

Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8850-5. doi: 10.1073/pnas.151261398. Epub 2001 Jul 3.


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.

MeSH terms

  • Alzheimer Disease / blood
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Amyloid beta-Peptides / immunology
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / metabolism*
  • Brain / metabolism*
  • Central Nervous System / metabolism*
  • Disease Models, Animal
  • Humans
  • Mice
  • Mice, Transgenic
  • Peptide Fragments / cerebrospinal fluid
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism*


  • Amyloid beta-Peptides
  • Antibodies, Monoclonal
  • Peptide Fragments
  • amyloid beta-protein (1-40)