A Cholesterol-Lowering Drug Reduces β-Amyloid Pathology in a Transgenic Mouse Model of Alzheimer's Disease

L.M. Refolo; 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

Neurobiology of Disease (Oct 2001)

A Cholesterol-Lowering Drug Reduces β-Amyloid Pathology in a Transgenic Mouse Model of Alzheimer's Disease

L.M. Refolo,
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

Affiliations

L.M. Refolo: Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York, 10962; University of Southern Alabama Medical School, Mobile, Alabama; University of Medicine and Dentistry of New Jersey/New Jersey Veterans Administration, Orange, New Jersey; The Rockefeller University, New York, New York; Jansens Research Foundation, Beerse, Belgium
M.A. Pappolla: Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York, 10962; University of Southern Alabama Medical School, Mobile, Alabama; University of Medicine and Dentistry of New Jersey/New Jersey Veterans Administration, Orange, New Jersey; The Rockefeller University, New York, New York; Jansens Research Foundation, Beerse, Belgium
J. LaFrancois: Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York, 10962; University of Southern Alabama Medical School, Mobile, Alabama; University of Medicine and Dentistry of New Jersey/New Jersey Veterans Administration, Orange, New Jersey; The Rockefeller University, New York, New York; Jansens Research Foundation, Beerse, Belgium
B. Malester: Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York, 10962; University of Southern Alabama Medical School, Mobile, Alabama; University of Medicine and Dentistry of New Jersey/New Jersey Veterans Administration, Orange, New Jersey; The Rockefeller University, New York, New York; Jansens Research Foundation, Beerse, Belgium
S.D. Schmidt: Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York, 10962; University of Southern Alabama Medical School, Mobile, Alabama; University of Medicine and Dentistry of New Jersey/New Jersey Veterans Administration, Orange, New Jersey; The Rockefeller University, New York, New York; Jansens Research Foundation, Beerse, Belgium
T. Thomas-Bryant: Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York, 10962; University of Southern Alabama Medical School, Mobile, Alabama; University of Medicine and Dentistry of New Jersey/New Jersey Veterans Administration, Orange, New Jersey; The Rockefeller University, New York, New York; Jansens Research Foundation, Beerse, Belgium
G.S. Tint: Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York, 10962; University of Southern Alabama Medical School, Mobile, Alabama; University of Medicine and Dentistry of New Jersey/New Jersey Veterans Administration, Orange, New Jersey; The Rockefeller University, New York, New York; Jansens Research Foundation, Beerse, Belgium
R. Wang: Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York, 10962; University of Southern Alabama Medical School, Mobile, Alabama; University of Medicine and Dentistry of New Jersey/New Jersey Veterans Administration, Orange, New Jersey; The Rockefeller University, New York, New York; Jansens Research Foundation, Beerse, Belgium
M. Mercken: Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York, 10962; University of Southern Alabama Medical School, Mobile, Alabama; University of Medicine and Dentistry of New Jersey/New Jersey Veterans Administration, Orange, New Jersey; The Rockefeller University, New York, New York; Jansens Research Foundation, Beerse, Belgium
S.S. Petanceska: Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York, 10962; University of Southern Alabama Medical School, Mobile, Alabama; University of Medicine and Dentistry of New Jersey/New Jersey Veterans Administration, Orange, New Jersey; The Rockefeller University, New York, New York; Jansens Research Foundation, Beerse, Belgium
K.E. Duff: Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York, 10962; University of Southern Alabama Medical School, Mobile, Alabama; University of Medicine and Dentistry of New Jersey/New Jersey Veterans Administration, Orange, New Jersey; The Rockefeller University, New York, New York; Jansens Research Foundation, Beerse, Belgium

Journal volume & issue: Vol. 8, no. 5
pp. 890 – 899

Abstract

Read online

Clinical, epidemiological, and laboratory studies suggest that cholesterol may play a role in the pathogenesis of Alzheimer's disease (AD). Transgenic mice exhibiting an Alzheimer's β-amyloid phenotype were treated with the cholesterol-lowering drug BM15.766 and tested for modulation of β-amyloid levels. BM15.766 treatment reduced plasma cholesterol, brain Aβ peptides, and β-amyloid load by greater than twofold. A strong, positive correlation between the amount of plasma cholesterol and Aβ 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 Aβ accumulation suggesting that lowering cholesterol by pharmacological means may be an effective approach for reducing the risk of developing AD.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

About the journal