Rapid cerebral amyloid binding by Aβ antibodies infused into β-amyloid precursor protein transgenic mice

Biol Psychiatry. 2010 Nov 15;68(10):971-4. doi: 10.1016/j.biopsych.2010.01.030. Epub 2010 Mar 31.


Background: Passive immunization for the treatment of Alzheimer's disease (AD) was rapidly translated into clinical trials. However, basic mechanisms of AD immunotherapy remain only partially understood.

Methods: We analyzed the dynamic changes of amyloid-β (Aβ) levels in plasma, brain, and cerebrospinal fluid (CSF) as well as cerebral amyloid binding by Aβ antibody after a single β1-antibody infusion into APP(Swedish) and APP(wildtype) transgenic mice at preplaque and plaque-bearing age.

Results: Following intravenous Aβ antibody treatment, plasma Aβ increased rapidly, reaching significantly higher levels in preplaque compared with plaque-bearing mice, whereas cerebral and CSF Aβ remained unchanged. Strikingly, Aβ antibodies exhibited strong cerebral amyloid plaque binding rapidly after intravenous administration in a subset of animals with more severe vascular amyloid.

Conclusions: Rapid plasma Aβ increase after Aβ antibody infusion results primarily from stabilization of Aβ. Nevertheless, the smaller plasma Aβ increase in plaque-bearing mice might be of diagnostic use. Importantly, intravenously administered antibodies can rapidly bind to cerebral plaques, potentially facilitated by vascular-amyloid-mediated damage of the blood-brain barrier.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Amyloid beta-Peptides / immunology*
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Protein Precursor / genetics*
  • Animals
  • Brain / immunology
  • Brain / metabolism*
  • Brain / pathology
  • Female
  • Humans
  • Immunoglobulin G / administration & dosage
  • Immunoglobulin G / immunology*
  • Infusions, Intravenous
  • Male
  • Mice
  • Mice, Transgenic
  • Plaque, Amyloid / immunology
  • Plaque, Amyloid / metabolism*


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Immunoglobulin G