Journal article
Rapid cerebral amyloid binding by Aβ antibodies infused into β-amyloid precursor protein transgenic mice.
- Winkler DT Department of Neurology, University Hospital Basel, Basel, Switzerland. winklerd@uhbs.ch
- Abramowski D
- Danner S
- Zurini M
- Paganetti P
- Tolnay M
- Staufenbiel M
- 2010-04-03
Published in:
- Biological psychiatry. - 2010
Age Factors
Amyloid beta-Peptides
Amyloid beta-Protein Precursor
Animals
Brain
Female
Humans
Immunoglobulin G
Infusions, Intravenous
Male
Mice
Mice, Transgenic
Plaque, Amyloid
English
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.
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.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1016/j.biopsych.2010.01.030
- PMID 20359696
- Persistent URL
- https://sonar.ch/global/documents/15375
Statistics
Document views: 6
File downloads: