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Comment on "ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models"

BIBLIOGRAPHIC THERAPEUTIC AGENT ANIMAL MODEL EXPERIMENTAL DESIGN OUTCOMES

Bibliographic

Year of Publication:
2013
Contact PI Name:
Radosveta Koldamova
Contact PI Affiliation:
Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Co-Authors:
Nicholas F. Fitz, Andrea A. Cronican, Iliya Lefterov
Primary Reference (PubMED ID):
23704552
Funding Source:
National Institute on Aging (NIA)
Alzheimer's Association
Study Goal and Principal Findings:

The goal of this study was to further assess the therapeutic potential of bexarotene and replicate the results reported by Cramer et al, 2013. In summary, the study shows that bexarotene significantly improved cognitive deficits in APP/PS1DE9 mice expressing human APOE3 and APOE4. In addition, the authors also found a significant decrease of ISF beta amyloid peptides Abeta in both APOE isoforms and a decrease in Abeta oligomers.  However, the effect of bexarotene on beta amyloid  peptides and beta amyloid plaques in cortex and hippocampus could not be confirmed. It should be noted that in this study the authors used a formulation (0.2 mg/kg glycerol) that differed from that used by Cramer et al, 2013.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Bexarotene
PubMed
PubChem
DrugBank
ClinicalTrials
Patents
Therapeutic Target:
Retinoid X Receptors (RXRs)
Open Targets
Pharos

Animal Model

Model Information:
Species:
Mouse
Model Type:
APPxPS1xApoE
Model Name:
APP695sw/PS1dE9/ApoE3
PubMed
Strain/Genetic Background:
Not Reported
Species:
Mouse
Model Type:
APPxPS1xApoE
Model Name:
APP695sw/PS1dE9/ApoE4
PubMed
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
Biomarkers
Dose
Formulation
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
Experiment Notes

It should be noted that in this study the authors used a formulation (0.2 mg/kg glycerol) that differed from that used by Cramer et al, 2013.

Outcomes

Outcome Measured
Outcome Parameters
Behavioral
Radial Arm Water Maze
Novel Object Recognition Test (NORT)
Histopathology
beta Amyloid Load
Biochemical
ISF-beta Amyloid Peptide 40
ISF-beta Amyloid Peptide 42
Brain-beta Amyloid Oligomers
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42
Pharmacodynamics
Target Engagement (Increased ATP Binding Cassette Subfamily A Member 1 Level)
Target Engagement (Increased Apolipoprotein E Level)
Toxicology
Body Weight
General Behavior
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