Targeting amyloid-β peptide (Aβ) oligomers by passive immunization with a conformation-selective monoclonal antibody improves learning and memory in Aβ precursor protein (APP) transgenic mice


BIBLIOGRAPHIC THERAPEUTIC AGENT ANIMAL MODEL EXPERIMENTAL DESIGN OUTCOMES

Bibliographic

Year of Publication:
2006
Contact PI Name:
Virginia M-Y. Lee
Contact PI Affiliation:
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Co-Authors:
Edward B. Lee, Lewis Z. Leng, Bin Zhang, Linda Kwong, John Q. Trojanowski, Ted Abel
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
Study Goal and Principal Findings:

Passive immunization of murine models of Alzheimer disease amyloidosis reduces amyloid-β peptide (Aβ) levels and improves cognitive function. To specifically address the role of Aβ oligomers in learning and memory, they generated a novel monoclonal antibody, NAB61, that preferentially recognizes a conformational epitope present in dimeric, small oligomeric, and higher order Aβ structures but not full-length amyloid-β precursor protein or C-terminal amyloid-β precursor protein fragments. NAB61 also recognized a subset of brain Aβ deposits, preferentially mature senile plaques, and amyloid angiopathy. Using NAB61 as immunotherapy, this study showed that aged Tg2576 transgenic mice treated with NAB61 displayed significant improvements in spatial learning and memory relative to control mice. These data implicated Aβ oligomers as a pathologic substrate for cognitive decline in Alzheimer disease.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Immunotherapy(passive)
Therapeutic Agent:
NAB61
Therapeutic Target:
beta Amyloid Peptide

Animal Model

Model Information:
Species:
Mouse
Model Type:
APP
Strain/Genetic Background:
C57B6/SJL
Species:
Mouse
Model Type:
Non-transgenic
Strain/Genetic Background:
C57B6/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
Behavioral
Morris Water Maze
Biomarker
Plasma-beta Amyloid Peptides
Biochemical
Binding-beta Amyloid Oligomers
Amyloid Precursor Protein (APP)
APP-CTF83 (CTF alpha)
APP-CTF99 (CTF beta)
Brain-beta Amyloid Deposits
Plasma-beta Amyloid Peptides
Brain-Buffer Soluble beta Amyloid Peptides
Brain-Formic Acid Soluble beta Amyloid Peptides
Immunochemistry
Amyloid Precursor Protein (APP)
Brain-beta Amyloid Deposits
Immunology
Antibody Target Specificity
Pharmacodynamics
Target Engagement (Reduction beta Amyloid Peptides-Brain)

Source URL: http://alzped.nia.nih.gov/targeting-amyloid-β-peptide-aβ