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

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-...

Full description

Bibliographic Details
Main Authors:	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
Format:	Article
Language:	English
Published:	Elsevier 2001-10-01
Series:	Neurobiology of Disease
Online Access:	http://www.sciencedirect.com/science/article/pii/S096999610190422X

id	doaj-12bdc1b469f74658871dafb93418b49e
record_format	Article
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	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
spellingShingle	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 A Cholesterol-Lowering Drug Reduces β-Amyloid Pathology in a Transgenic Mouse Model of Alzheimer's Disease Neurobiology of Disease
author_facet	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
author_sort	L.M. Refolo
title	A Cholesterol-Lowering Drug Reduces β-Amyloid Pathology in a Transgenic Mouse Model of Alzheimer's Disease
title_short	A Cholesterol-Lowering Drug Reduces β-Amyloid Pathology in a Transgenic Mouse Model of Alzheimer's Disease
title_full	A Cholesterol-Lowering Drug Reduces β-Amyloid Pathology in a Transgenic Mouse Model of Alzheimer's Disease
title_fullStr	A Cholesterol-Lowering Drug Reduces β-Amyloid Pathology in a Transgenic Mouse Model of Alzheimer's Disease
title_full_unstemmed	A Cholesterol-Lowering Drug Reduces β-Amyloid Pathology in a Transgenic Mouse Model of Alzheimer's Disease
title_sort	cholesterol-lowering drug reduces β-amyloid pathology in a transgenic mouse model of alzheimer's disease
publisher	Elsevier
series	Neurobiology of Disease
issn	1095-953X
publishDate	2001-10-01
description	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.
url	http://www.sciencedirect.com/science/article/pii/S096999610190422X
work_keys_str_mv	AT lmrefolo acholesterolloweringdrugreducesbamyloidpathologyinatransgenicmousemodelofalzheimersdisease AT mapappolla acholesterolloweringdrugreducesbamyloidpathologyinatransgenicmousemodelofalzheimersdisease AT jlafrancois acholesterolloweringdrugreducesbamyloidpathologyinatransgenicmousemodelofalzheimersdisease AT bmalester acholesterolloweringdrugreducesbamyloidpathologyinatransgenicmousemodelofalzheimersdisease AT sdschmidt acholesterolloweringdrugreducesbamyloidpathologyinatransgenicmousemodelofalzheimersdisease AT tthomasbryant acholesterolloweringdrugreducesbamyloidpathologyinatransgenicmousemodelofalzheimersdisease AT gstint acholesterolloweringdrugreducesbamyloidpathologyinatransgenicmousemodelofalzheimersdisease AT rwang acholesterolloweringdrugreducesbamyloidpathologyinatransgenicmousemodelofalzheimersdisease AT mmercken acholesterolloweringdrugreducesbamyloidpathologyinatransgenicmousemodelofalzheimersdisease AT sspetanceska acholesterolloweringdrugreducesbamyloidpathologyinatransgenicmousemodelofalzheimersdisease AT keduff acholesterolloweringdrugreducesbamyloidpathologyinatransgenicmousemodelofalzheimersdisease AT lmrefolo cholesterolloweringdrugreducesbamyloidpathologyinatransgenicmousemodelofalzheimersdisease AT mapappolla cholesterolloweringdrugreducesbamyloidpathologyinatransgenicmousemodelofalzheimersdisease AT jlafrancois cholesterolloweringdrugreducesbamyloidpathologyinatransgenicmousemodelofalzheimersdisease AT bmalester cholesterolloweringdrugreducesbamyloidpathologyinatransgenicmousemodelofalzheimersdisease AT sdschmidt cholesterolloweringdrugreducesbamyloidpathologyinatransgenicmousemodelofalzheimersdisease AT tthomasbryant cholesterolloweringdrugreducesbamyloidpathologyinatransgenicmousemodelofalzheimersdisease AT gstint cholesterolloweringdrugreducesbamyloidpathologyinatransgenicmousemodelofalzheimersdisease AT rwang cholesterolloweringdrugreducesbamyloidpathologyinatransgenicmousemodelofalzheimersdisease AT mmercken cholesterolloweringdrugreducesbamyloidpathologyinatransgenicmousemodelofalzheimersdisease AT sspetanceska cholesterolloweringdrugreducesbamyloidpathologyinatransgenicmousemodelofalzheimersdisease AT keduff cholesterolloweringdrugreducesbamyloidpathologyinatransgenicmousemodelofalzheimersdisease
_version_	1724212203749376000
spelling	doaj-12bdc1b469f74658871dafb93418b49e2021-03-20T04:47:13ZengElsevierNeurobiology of Disease1095-953X2001-10-0185890899A Cholesterol-Lowering Drug Reduces β-Amyloid Pathology in a Transgenic Mouse Model of Alzheimer's DiseaseL.M. Refolo0M.A. Pappolla1J. LaFrancois2B. Malester3S.D. Schmidt4T. Thomas-Bryant5G.S. Tint6R. Wang7M. Mercken8S.S. Petanceska9K.E. Duff10Nathan 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, BelgiumNathan 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, BelgiumNathan 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, BelgiumNathan 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, BelgiumNathan 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, BelgiumNathan 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, BelgiumNathan 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, BelgiumNathan 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, BelgiumNathan 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, BelgiumNathan 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, BelgiumNathan 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, BelgiumClinical, 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.http://www.sciencedirect.com/science/article/pii/S096999610190422X

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

Similar Items