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Passive amyloid immunotherapy clears amyloid and transiently activates microglia in a transgenic mouse model of amyloid deposition


Year of Publication:
Contact PI Name:
David Morgan
Contact PI Affiliation:
Department of Pharmacology, University of South Florida, Tampa, Florida, USA
Donna M. Wilcock, Amyn Rojiani, Arnon Rosenthal, Gil Levkowitz, Sangeetha Subbarao, Jennifer Alamed, David Wilson, Nedda Wilson, Melissa J. Freeman, Marcia N. Gordon
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
Study Goal and Principal Findings:

The role of microglia in the removal of amyloid deposits after systemically administered anti-Abeta antibodies remains unclear. In the current study, were injected Tg2576 APP transgenic mice weekly with an anti-Abeta antibody for 1, 2, or 3 months such that all mice were 22 months at the end of the study. In mice immunized for 3 months, was found an improvement in alternation performance in the Y maze. Histologically, was detected mouse IgG bound to congophilic amyloid deposits in those mice treated with the anti-Abeta antibody but not in those treated with a control antibody. Was found that Fcgamma receptor expression on microglia was increased after 1 month of treatment, whereas CD45 was increased after 2 months of treatment. Associated with these microglial changes was a reduction in both diffuse and compact amyloid deposits after 2 months of treatment. Interestingly, the microglia markers were reduced to control levels after 3 months of treatment, whereas amyloid levels remained reduced. Serum Abeta levels and anti-Abeta antibody levels were elevated to similar levels at all three survival times in mice given anti-Abeta injections rather than control antibody injections. These data show that the antibody is able to enter the brain and bind to the amyloid deposits, likely opsonizing the Abeta and resulting in Fcgamma receptor-mediated phagocytosis. Together with earlier work, this data argue that all proposed mechanisms of anti-Abeta antibody-mediated amyloid removal can be simultaneously active.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Immunotherapy(passive)
Therapeutic Agent:
2286 (anti-Abeta 28-40 Mab)
Therapeutic Target:
beta Amyloid Peptide

Animal Model

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

Experimental Design

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


Outcome Measured
Outcome Parameters
Y Maze
Congophillic Amyloid Deposits
Activated Microglia
Dense-core/Compact Plaques
Anti-beta Amyloid Binding
Brain-beta Amyloid Peptide-Total
Fc gamma Receptor
Brain-beta Amyloid Peptides
Serum-beta Amyloid Peptides
Antibody Concentration-Plasma
Blood Brain Barrier Penetration
Target Engagement (Reduction beta Amyloid Peptides-Brain)
Target Engagement (Complex of Antibody with Amyloid-Brain)