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Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse


Year of Publication:
Contact PI Name:
Dale Schenk
Contact PI Affiliation:
Elan Pharmaceuticals, South San Francisco, California, USA
Robin Barbour, Whitney Dunn, Grace Gordon, Henry Grajeda, Teresa Guido, Kang Hu, Jiping Huang, Kelly Johnson-Wood, Karen Khan, Dora Kholodenko, et al
Primary Reference (PubMED ID):
Funding Source:
Not Reported
Study Goal and Principal Findings:

In this study, PDAPP transgenic animals were immunized with Abeta 42, in young animals (6 weeks) before the onset of AD-type neuropathologies and, older animals (11 months), when amyloid-beta deposition and several of the subsequent neuropathological changes are well established. In summary, data presented showed that outcomes of Abeta-plaque burden, neuritic dystrophy and gliosis were all significantly improved by Abeta 42 immunization in both young and old animals. Immunization preceding plaque development profoundly affected the occurrence of new lesions, as the progression of beta-amyloidosis and associated neuropathology was essentially wholly blocked. Amyloid-beta 42 immunization also significantly retarded the progression of existing pathology in affected regions of the older animals. Collectively, the results suggest that amyloid-beta immunization may prove beneficial for both the treatment and prevention of Alzheimer's disease.

Bibliographic Notes:
Full Author List: Dale Schenk, Robin Barbour, Whitney Dunn, Grace Gordon, Henry Grajeda, Teresa Guido, Kang Hu, Jiping Huang, Kelly Johnson-Wood, Karen Khan, Dora Kholodenko, Mike Lee, Zhenmei Liao, Ivan Lieberburg, Ruth Motter, Linda Mutter, Ferdie Soriano, George Shopp, Nicki Vasquez, Christopher Vandevert, Shannan Walker, Mark Wogulis, Ted Yednock, Dora Games and Peter Seubert.

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
Activated Astrocytes
Dystrophic Neurites
Brain-beta Amyloid Peptide-Total
Anti-beta Amyloid Peptide 42 Antibody Titers