Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease

Bibliographic

Year of Publication: 
2000
Contact PI Name: 
Frederique Bard
Contact PI Affiliation: 
Elan Pharmaceuticals, South San Francisco, California, USA
Co-Authors: 
Catherine Cannon, Robin Barbour, Rae-Lyn Burke, Dora Games, Henry Grajeda, Terasa Guido, Kang Hu, Jiping Huang, Kelly Johnson-Wood, Karen Khan, et al
Primary Reference (PubMED ID): 
Funding Source:
Study Goal and Principal Findings: 

The overarching goal of this study was to test the hypothesis that peripheral administration of antibodies against amyloid beta-peptide would be  sufficient to reduce beta amyloid burden in a mouse model of AD. In summary this study presented evidence that: 1) that passively administered antibodies against Aβ peptide reduced the extent of beta amyloid plaque deposition in the PDAPP mouse model of AD; 2)despite their relatively modest serum levels, the passively administered antibodies were able to enter the central nervous system, decorate plaques and induce clearance of preexisting beta amyloid; 3)antibody entry into the CNS was not due to abnormal leakage of the blood–brain barrier, as there was no increase in vascular permeability in PDAPP mice. In addition, when examined in an ex vivo assay with sections of PDAPP or Alzheimer disease brain tissue, antibodies against amyloid β-peptide triggered microglial cells to clear plaques through Fc receptor-mediated phagocytosis and subsequent peptide degradation. These results indicate that antibodies can cross the blood–brain barrier to act directly in the central nervous system and should be considered as a therapeutic approach for the treatment of Alzheimer disease and other neurological disorders.

Bibliographic Notes: 
Full Author List: Frédérique Bard, Catherine Cannon, Robin Barbour, Rae-Lyn Burke, Dora Games, Henry Grajeda, Teresa Guido, Kang Hu, Jiping Huang, Kelly Johnson-Wood, Karen Khan, Dora Kholodenko, Mike Lee, Ivan Lieberburg, Ruth Motter, Minh Nguyen, Ferdie Soriano, Nicki Vasquez, Kim Weiss, Brent Welch, Peter Seubert, Dale Schenk and Ted Yednock.

Therapeutic Agent

Therapeutic Information: 
Therapy Type:
Therapy Type:
Therapy Type:
Therapy Type:

Animal Model

Model Information: 
Species:
Model Type:
Strain/Genetic Background: 
Not Reported

Experimental Design

Is the following information reported in the study?: 
Power/Sample Size Calculation
Blinded for Treatment
Pharmacokinetic Measures
Toxicology Measures
Biomarkers
Formulation
Duration of Treatment
Age of Animal at the Beginning of Treatment
Sex as a Biological Variable
Number of Premature Deaths
Statistical Plan
Inclusion/Exclusion Criteria Included
Randomized into Groups
Blinded for Outcome Measures
Pharmacodynamic Measures
ADME Measures
Dose
Route of Delivery
Frequency of Administration
Age of Animal at the End of Treatment
Study Balanced for Sex as a Biological Variable
Number of Excluded Animals
Genetic Background
Conflict of Interest

Outcomes

Outcomes: 
Outcome MeasuredOutcome Parameters
Histopathology
  • beta Amyloid Load
  • Immunology
  • T Cell Response
  • Pharmacodynamics
  • Target Engagement (Binding Antibody-Sera to beta Amyloid Deposits)