Anti-Aβ42– and anti-Aβ40–specific mAbs attenuate amyloid deposition in an Alzheimer disease mouse model


BIBLIOGRAPHIC THERAPEUTIC AGENT ANIMAL MODEL EXPERIMENTAL DESIGN OUTCOMES

Bibliographic

Year of Publication:
2006
Contact PI Name:
Todd E. Golde
Contact PI Affiliation:
Department of Neuroscience, Mayo Clinic, Mayo Clinic College of Medicine, Jacksonville, Florida
Co-Authors:
Yona Levites, Pritam Das, Robert W. Price, Marjorie J. Rochette, Lisa A. Kostura, Eileen M. McGowan, Michael P. Murphy
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
Mayo Foundation
Study Goal and Principal Findings:

Accumulation and aggregation of amyloid β peptide 1–42 (Aβ42) in the brain has been hypothesized as triggering a pathological cascade that causes Alzheimer disease (AD). To determine whether selective targeting of Aβ42 versus Aβ40 or total Aβ is an effective way to prevent or treat AD, this study compared the effects of passive immunization with an anti-Aβ42 mAb, an anti-Aβ40 mAb, and multiple Aβ1–16 mAbs. This study established in vivo binding selectivity of the anti-Aβ42 and anti-Aβ40 mAbs using novel TgBRI-Aβ mice. They then conducted a prevention study in which the anti-Aβ mAbs were administered to young Tg2576 mice, which have no significant Aβ deposition, and therapeutic studies in which mAbs were administered to Tg2576 or CRND8 mice with modest levels of preexisting Aβ deposits. Anti-Aβ42, anti-Aβ40, and anti-Aβ1–16 mAbs attenuated plaque deposition in the prevention study. In contrast, anti-Aβ42 and anti-Aβ40 mAbs were less effective in attenuating Aβ deposition in the therapeutic studies and were not effective in clearing diffuse plaques following direct injection into the cortex. These data suggest that selective targeting of Aβ42 or Aβ40 may be an effective strategy to prevent amyloid deposition, but may have limited benefit in a therapeutic setting.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Immunotherapy(passive)
Therapeutic Agent:
Ab42.2 (anti-Abeta x-42 Mab)
Therapeutic Target:
beta Amyloid Peptide
Therapy Type:
Biologic - Immunotherapy(passive)
Therapeutic Agent:
Ab40.1 (anti-Abeta x-40 Mab)
Therapeutic Target:
beta Amyloid Peptide
Therapy Type:
Biologic - Immunotherapy(passive)
Therapeutic Agent:
Ab2 (anti-Abeta 1-16 Mab)
Therapeutic Target:
beta Amyloid Peptide
Therapy Type:
Biologic - Immunotherapy(passive)
Therapeutic Agent:
Ab3 (anti-Abeta 1-16 Mab)
Therapeutic Target:
beta Amyloid Peptide
Therapy Type:
Biologic - Immunotherapy(passive)
Therapeutic Agent:
Ab5 (anti-Abeta 1-16 Mab)
Therapeutic Target:
beta Amyloid Peptide
Therapy Type:
Biologic - Immunotherapy(passive)
Therapeutic Agent:
Ab9 (anti-Abeta 1-16 Mab)
Therapeutic Target:
beta Amyloid Peptide

Animal Model

Model Information:
Species:
Mouse
Model Type:
APP
Strain/Genetic Background:
B6C3F1/Tac
Species:
Mouse
Model Type:
APP
Strain/Genetic Background:
B6/SJL

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
Biomarkers
Dose
Formulation
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

Outcomes

Outcome Measured
Outcome Parameters
Histopathology
beta Amyloid Deposits
Dense-core/Compact Plaques
Cerebral Amyloid Angiopathy (CAA)
Biochemical
Brain-Detergent Soluble beta Amyloid Peptides
Brain-Formic Acid Soluble beta Amyloid Peptides
Brain-beta Amyloid Peptide-Total
Immunochemistry
Cerebral Amyloid Angiopathy (CAA)
Brain-beta Amyloid Deposits
Immunology
Antibody Target Specificity
Biomarker
Plasma-Complex of Antibody and beta Amyloid
Pharmacodynamics
Target Engagement (Clearance beta Amyloid Deposits)
Target Engagement (Binding beta Amyloid Antibodies to beta Amyloid Deposits)

Source URL: http://alzped.nia.nih.gov/anti-aβ42–-and-anti-aβ40