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Immunization with a nontoxic/nonfibrillar amyloid-β homologous peptide reduces Alzheimer’s disease-associated pathology in transgenic mice


Year of Publication:
Contact PI Name:
Einar M. Sigurdsson
Contact PI Affiliation:
Department of Neurology, New York University School of Medicine, New York, USA
Henrieta Scholtzova, Pankaj D. Mehta, Blas Frangione, Thomas Wisniewski
Primary Reference (PubMED ID):
Funding Source:
Metlife Award
National Institute on Aging (NIA)
Study Goal and Principal Findings:

Transgenic mice with brain amyloid-β (Aβ) plaques immunized with aggregated Aβ1-42 have reduced cerebral amyloid burden. However, the use of Aβ1-42 in humans may not be appropriate because it crosses the blood brain barrier, forms toxic fibrils, and can seed fibril formation. They report that immunization in transgenic APP mice (Tg2576) for 7 months with a soluble nonamyloidogenic, nontoxic Aβ homologous peptide reduced cortical and hippocampal brain amyloid burden by 89% (P = 0.0002) and 81% (P = 0.0001), respectively. Concurrently, brain levels of soluble Aβ1-42 were reduced by 57% (P = 0.0019). Ramified microglia expressing interleukin-1β associated with the Aβ plaques were absent in the immunized mice indicating reduced inflammation in these animals. These promising findings suggest that immunization with nonamyloidogenic Aβ derivatives represents a potentially safer therapeutic approach to reduce amyloid burden in Alzheimer’s disease, instead of using toxic Aβ fibrils.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Immunotherapy(active)
Therapeutic Agent:
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
Activated Astrocytes
Congophillic Amyloid Deposits
beta Amyloid Deposits
Activated Microglia
Neuronal Loss
Brain-Buffer Soluble beta Amyloid Peptides
Brain-Buffer Soluble beta Amyloid Peptide 40
Brain-Buffer Soluble beta Amyloid Peptide 42
beta Amyloid Aggregation
Glial Fibrillary Acidic Protein (GFAP)
Brain-beta Amyloid Deposits
Interleukin 1 beta (IL-1 beta)
Circular Dichroism
Cell Biology
Cell Viability
Antibody Titers
Target Engagement (Reduction beta Amyloid Peptides-Brain)
Cell Viability