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Antibody-mediated clearance of amyloid-beta peptide from cerebral amyloid angiopathy revealed by quantitative in vivo imaging


Year of Publication:
Contact PI Name:
Brian J. Bacskai
Contact PI Affiliation:
Department of Neurology/Alzheimer Research Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA
Claudia M. Prada, Monica Garcia-Alloza, Rebecca A. Betensky, Sandy X. Zhang-Nunes, Steven M. Greenberg, Matthew P. Frosch
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
Harvard Center for Neurodegeneration and Repair
Howard Hughes Medical Institute
Study Goal and Principal Findings:

Cerebral amyloid angiopathy (CAA) is the accumulation of amyloid-beta peptide (Abeta) in the vessel wall of arteries in the brain. Because CAA is commonly associated with Alzheimer's disease (AD), characterized by parenchymal deposition of the same peptide in the form of senile plaques, there is considerable interest in the relationship of the two deposits in generating human disease. The study of CAA is of particular importance for immunotherapeutic approaches to AD, because reports of anti-Abeta immunotherapy in mice and humans have suggested that, whereas CAA appeared resistant to clearance, its response to this treatment promoted potential adverse effects, including meningoencephalitis. Was used multiphoton microscopy and longitudinal imaging to monitor CAA in a mouse model of amyloid deposition to evaluate the effects of anti-Abeta passive immunotherapy. Was found detectable clearance of CAA deposits within 1 week after a single administration of antibody directly to the brain, an effect that was short-lived. Chronic administration of antibody over 2 weeks led to more robust clearance without evidence of hemorrhage or other destructive changes. Was found that the progressive clearance of Abeta from vessels follows distinct kinetics from what has been previously reported for clearance of plaques (parenchymal deposits of Abeta). This quantitative in vivo imaging approach directly demonstrates that CAA in a transgenic mouse model can be cleared with an optimized immunotherapy.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Immunotherapy(passive)
Therapeutic Agent:
10D5 (anti-Abeta 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
Cerebral Amyloid Angiopathy (CAA)
Dense-core/Compact Plaques
beta Amyloid Deposits
beta Amyloid Load
Multiphoton Microscopy
Target Engagement (Clearance beta Amyloid Deposits)