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Reduced effectiveness of Abeta1-42 immunization in APP transgenic mice with significant amyloid deposition


Year of Publication:
Contact PI Name:
Todd E. Golde
Contact PI Affiliation:
Department of Neurosciences, Mayo Clinic Jacksonville, Jacksonville, Florida, USA
Pritam Das, M. Paul Murphy, Linda H. Younkin, Steven G. Younkin
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
American Federation for Aging Research
Ellison Medical Foundation
John Douglas French Foundation
Study Goal and Principal Findings:

Vaccinations with Abeta1-42 have been shown to reduce amyloid burden, and improve cognition in transgenic models of Alzheimer's disease (AD).The goal of this study was to test the efficacy of Abeta1–42 immunization in Tg2576 (model of AD) mice with varying degrees of amyloid burden at the time of immunization. Results demonstrate that Abeta1–42 immunization of Tg2576 mice was effective in reducing amyloid burden in young mice but did, not significantly alter beta- amyloid burden in older Tg2576 mice. Furthermore, in contrast with reports on the PDAPP mice, immunization of Tg2576 mice with Abeta1–42 appeared to be more effective in reducing Abeta 42 than Abeta 40. This selectivity is most apparent in the older Tg2576 mice with heavy amyloid loads, where Abeta1–42 immunization only reduced Abeta 42 levels without altering Abeta 40 levels or beta amyloid plaque load. 

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Immunotherapy(active)
Therapeutic Agent:
beta Amyloid Peptide 1-42
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
beta Amyloid Load
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42
Anti-beta Amyloid Peptide 42 Antibody Titers
Antibody Isotypes
Target Engagement (Binding Antibody-Sera to beta Amyloid Deposits)