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Treatment with an amyloid-β antibody ameliorates plaque load, learning deficits, and hippocampal long-term potentiation in a mouse model of Alzheimer’s disease


Year of Publication:
Contact PI Name:
Richard E. Hartman
Contact PI Affiliation:
Departments of Neurology and Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA
Yukitoshi Izumi, Kelly R. Bales, Steven M. Paul, David F. Wozniak, David M. Holtzman
Primary Reference (PubMED ID):
Funding Source:
National Institute on Drug Abuse (NIDA)
National Institute on Aging (NIA)
Eli Lilly and Company
National Institute of Neurological Disorders and Stroke (NINDS)
Study Goal and Principal Findings:

PDAPP transgenic mice overexpress a mutant form of human amyloid precursor protein under control of the platelet-derived growth factor promoter in CNS neurons that causes early onset, familial Alzheimer’s disease in humans. These mice, on a mixed genetic background, have been shown to have substantial learning impairments from early ages, as well as an age-dependent decline in learning ability that has been hypothesized to be caused by amyloid-β (Aβ) accumulation. The goals of this study were to determine: (1) whether PDAPP mice on a pure C57BL/6 background develop more severe age-dependent learning deficits than wild-type mice; (2) if so, whether Aβ accumulation accounts for the excessive decline in learning ability; and (3) whether the learning deficits are reversible, even after significant Aβ deposition. At 4 – 6, 10 –12, or 17–19 months of age, PDAPP and littermate wild-type mice on a C57BL/6 background were tested on a 5 week water maze protocol in whichthe location of the escape platform changed weekly, requiringthe mice to repeatedly learn new information. PDAPP mice exhibited impaired spatial learning as early as 4 months (pre-Aβ deposition), and the performance of both wild-type and PDAPP mice declined with age. However, PDAPP mice exhibited significantly greater deterioration with age. Direct evidence for the role of Aβ accumulation in the age-related worsening in PDAPP mice was provided by the observation that systemic treatment over several weeks with the anti-Aβ antibody 10D5 reduced plaque deposition, increased plasma Aβ, improved hippocampal long-term potentiation, and improved behavioral performance in aged PDAPP mice with substantial Aβ burden.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Immunotherapy(passive)
Therapeutic Agent:
10D5 (anti-Abeta Mab)
Therapeutic Target:
beta Amyloid Peptide

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
Model Type:
Strain/Genetic Background:

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
Morris Water Maze
Spontaneous Activity
Plasma-beta Amyloid Peptide 40
Plasma-beta Amyloid Peptide 42
Brain-Buffer Insoluble beta Amyloid Peptide 40
Brain-Buffer Insoluble beta Amyloid Peptide 42
Brain-Buffer Soluble beta Amyloid Peptide 40
Brain-Buffer Soluble beta Amyloid Peptide 42
Fibrillar beta Amyloid Deposits
beta Amyloid Load
Dense-core/Compact Plaques
Long Term Potentiation (LTP)
Plasma-beta Amyloid Peptide 40
Plasma-beta Amyloid Peptide 42
Target Engagement (Reduction beta Amyloid Peptides-Brain)