• David T Winkler, Dorothee Abramowski, Simone Danner, Mauro Zurini, Paolo Paganetti, Markus Tolnay, and Matthias Staufenbiel.
• Department of Neurology, University Hospital Basel, Basel, Switzerland. winklerd@uhbs.ch
• Biol. Psychiatry. 2010 Nov 15;68(10):971-4.

BackgroundPassive 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.MethodsWe 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.ResultsFollowing 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.ConclusionsRapid 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.Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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