Rapid Cerebral Amyloid Binding by Aβ Antibodies Infused into β-Amyloid Precursor Protein Transgenic Mice

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 beta (A beta) levels in plasma brain and cerebrospinal fluid (CSF) as well as cerebral amyloid binding by A beta antibody after a single beta 1 antibody infusion into APP(Swedish) and APP(wildtype) transgenic mice at preplaque and plaque bearing age Results Following intravenous A beta antibody treatment plasma A beta increased rapidly reaching significantly higher levels in preplaque compared with plaque bearing mice whereas cerebral and CSF A beta remained unchanged Strikingly A beta antibodies exhibited strong cerebral amyloid plaque binding rapidly after intravenous administration in a subset of animals with more severe vascular amyloid Conclusions Rapid plasma A beta increase after A beta antibody infusion results primarily from stabilization of A beta Nevertheless the smaller plasma A beta 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