| First Author | Winkler DT | Year | 2010 |
| Journal | Biol Psychiatry | Volume | 68 |
| Issue | 10 | Pages | 971-4 |
| PubMed ID | 20359696 | Mgi Jnum | J:281423 |
| Mgi Id | MGI:6377993 | Doi | 10.1016/j.biopsych.2010.01.030 |
| Citation | Winkler DT, et al. (2010) Rapid cerebral amyloid binding by Abeta antibodies infused into beta-amyloid precursor protein transgenic mice. Biol Psychiatry 68(10):971-4 |
| abstractText | 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 (Abeta) levels in plasma, brain, and cerebrospinal fluid (CSF) as well as cerebral amyloid binding by Abeta antibody after a single beta1-antibody infusion into APP(Swedish) and APP(wildtype) transgenic mice at preplaque and plaque-bearing age. RESULTS: Following intravenous Abeta antibody treatment, plasma Abeta increased rapidly, reaching significantly higher levels in preplaque compared with plaque-bearing mice, whereas cerebral and CSF Abeta remained unchanged. Strikingly, Abeta antibodies exhibited strong cerebral amyloid plaque binding rapidly after intravenous administration in a subset of animals with more severe vascular amyloid. CONCLUSIONS: Rapid plasma Abeta increase after Abeta antibody infusion results primarily from stabilization of Abeta. Nevertheless, the smaller plasma Abeta 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. |
