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


Year of Publication:
Contact PI Name:
Gary E. Landreth
Contact PI Affiliation:
Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
Paige E. Cramer, John R. Cirrito, Daniel W. Wesson, C. Y. Daniel Lee, J. Colleen Karlo, Adriana E. Zinn, Brad T. Casali, Jessica L. Restivo, Whitney D. Goebel, Michael J. James, Kurt R. Brunden, Donald A. Wilson
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
National Institute of Neurological Disorders and Stroke (NINDS)
American Health Assistance Foundation
Blanchette Hooker Rockefeller Foundation
Roby and Taft Funds for Alzheimer's Research
Painstone Foundation
Thome Memorial Foundation
National Institute on Deafness and Other Communication Disorders (NIDCD)
Study Goal and Principal Findings:

In this study the authors tested the efficacy of the RXR agonists bexarotene (Targretin) in clearance of beta amyloid peptides from brains of AD Tg mouse models.  Oral administration of the RXR agonist bexarotene to a mouse model of AD resulted in enhanced clearance of soluble beta amyloid peptide within hours in an apoE-dependent manner, and beta amyloid plaque area was reduced more than 50% within just 72 hours. Furthermore, bexarotene stimulated the rapid reversal of cognitive, social, and olfactory deficits and improved neural circuit function. Thus, RXR activation stimulates physiological beta amyloid clearance mechanisms, resulting in the rapid reversal of a broad range of  beta amyloid-induced deficits.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Therapeutic Target:
Retinoid X Receptors (RXRs)

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
Not Reported
Model Type:
Strain/Genetic Background:
Not Reported
Model Type:
Strain/Genetic Background:
Not Reported
Animal Model Notes:
Mouse strains were not directly reported in the article. The supplemental materials contained the following three articles cited strain backgrounds of the original founder mice: J. L. Jankowsky et al., PLoS Med 2, e355 (2005), K. Hsiao et al., Science 274, 99 (1996), . R. Radde et al., EMBO Rep 7, 940 (2006).

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
Contextual Fear Conditioning
Morris Water Maze
Olfactory Cross Habituation
beta Amyloid Load
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42
ISF-beta Amyloid Peptide 40
ISF-beta Amyloid Peptide 42
Local Field Potentials (LFPs)
Cell Biology
beta Amyloid Peptide Clearance
Target Engagement (Increased Liver X Receptor)