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A cholesterol-lowering drug reduces beta-amyloid pathology in a transgenic mouse model of Alzheimer’s disease


Year of Publication:
Contact PI Name:
Lorenzo M. Refolo
Contact PI Affiliation:
Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York, USA
M.A. Pappolla, J. LaFrancois, B. Malester, S.D. Schmidt, T. Thomas-Bryant, G.S. Tint, R. Wang, M. Mercken, S.S. Petanceska, K.E. Duff
Primary Reference (PubMED ID):
Funding Source:
Alzheimer's Association
National Institute on Aging (NIA)
Alzheimer's Drug Discovery Foundation (ADDF)
Study Goal and Principal Findings:

The over-arching goal of this study was to determine the effects of a cholesterol-lowering drug BM15.766 on beta-amyloid pathology in the APPPS1 mouse model of Alzheimer's disease. BM15.766 treatment reduced plasma cholesterol, brain Abeta peptides, and beta-amyloid load by greater than twofold. A strong, positive correlation between the amounts of plasma cholesterol and Abeta was observed. Furthermore, drug treatment reduced the amyloidogenic processing of the amyloid precursor protein, suggesting alterations in processing in response to cholesterol modulation. This study demonstrates that hypocholesterolemia is associated with reduced Abeta accumulation suggesting that lowering cholesterol by pharmacological means may be an effective approach for reducing the risk of developing AD. 

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Therapeutic Target:
7-Dehydrocholesterol delta-7 Reductase

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
beta Amyloid Load
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42
Amyloid Precursor Protein (APP) Metabolites
Amyloid Precursor Protein (APP)
Brain-Total Cholesterol
Plasma-Total Cholesterol
Target Engagement (Reduction Total Cholesterol-Plasma)