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Comparison of efficacy of preventive and therapeutic vaccines targeting the N terminus of β-amyloid in an animal model of Alzheimer's disease


Year of Publication:
Contact PI Name:
Michael G. Agadjanyan
Contact PI Affiliation:
Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, California, USA
Irina Petrushina, Hayk Davtyan, Armine Hovakimyan, Arpine Davtyan, Giselle F. Passos, David H. Cribbs, Anahit Ghochikyan
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
National Institute of Neurological Disorders and Stroke (NINDS)
Alzheimer's Association
Study Goal and Principal Findings:

Previously, was reported that Alzheimer's disease (AD) epitope vaccines (EVs) composed of N-terminal β-amyloid (Aβ42) B cell epitope fused with universal foreign T helper (Th) epitope(s) were immunogenic, potent, and safe in different amyloid precursor protein (APP) transgenic mice with early AD-like pathology. However, developing an effective therapeutic vaccine is much more challenging, especially when a self-antigen such as Aβ42 is a target. Here, is directly compared the efficacy of anti-Aβ42 antibodies in Tg2576 mice with low or high levels of AD-like pathology at the start of immunizations: 6-6.5 months for preventive vaccinations and 16-19 months for therapeutic vaccinations. EV in a preventive setting induced high levels of anti-Aβ antibodies, significantly reducing pathologic forms of Aβ in the brains of Tg2576 mice. When used therapeutically for immunesenescent Tg2576 mice, EV induced low levels of antibodies not sufficient for clearing of AD-like pathology. Separately, was demonstrated that EV was also not effective in 11-11.5-month-old Tg2576 mice with moderate AD-like pathology. However, we augmented the titers of anti-Aβ antibodies in transgenic (Tg) mice of the same age possessing the pre-existing memory Th cells and detected a significant decrease in diffuse and core plaques in cortical regions compared to control animals along with improved novel object recognition performance.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Immunotherapy(active)
Therapeutic Agent:
N-terminal β-Amyloid (Aβ42) B Cell Epitope Vaccine
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
Novel Object Recognition Test (NORT)
Object Place Recognition
Activated Astrocytes
Activated Microglia
Fibrillar beta Amyloid Deposits
Dense-core/Compact Plaques
beta Amyloid Deposits
beta Amyloid Load
Cerebral Amyloid Angiopathy (CAA)
Brain-Buffer Soluble beta Amyloid Peptide 40
Brain-Buffer Soluble beta Amyloid Peptide 42
Activated Microglia
Activated Astrocytes
Glial Fibrillary Acidic Protein (GFAP)
Major Histocompatibility Antigens Class 2 (MHC II)
Brain-beta Amyloid Deposits
T Cells
T Cell Response
Antibody Target Specificity
Humoral Response
Antibody Titers
Anti-beta Amyloid Antibody Titers
Target Engagement (Reduction beta Amyloid Peptides-Brain)