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

L. M. Refolo, Miguel Pappolla, J. LaFrancois, B. Malester, S. D. Schmidt, T. Thomas-Bryant, G. S. Tint, R. Wang, M. Mercken, S. S. Petanceska, K. E. Duff

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)890-899
Number of pages10
JournalNeurobiology of Disease
Volume8
Issue number5
DOIs
StatePublished - 2001
Externally publishedYes

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Amyloid
Transgenic Mice
Alzheimer Disease
Cholesterol
Pathology
Pharmaceutical Preparations
Amyloid beta-Protein Precursor
Epidemiologic Studies
Pharmacology
Phenotype
Peptides
Brain

ASJC Scopus subject areas

  • Neurology

Cite this

Refolo, L. M., Pappolla, M., LaFrancois, J., Malester, B., Schmidt, S. D., Thomas-Bryant, T., ... Duff, K. E. (2001). A cholesterol-lowering drug reduces β-amyloid pathology in a transgenic mouse model of Alzheimer's disease. Neurobiology of Disease, 8(5), 890-899. https://doi.org/10.1006/nbdi.2001.0422

A cholesterol-lowering drug reduces β-amyloid pathology in a transgenic mouse model of Alzheimer's disease. / Refolo, L. M.; Pappolla, Miguel; LaFrancois, J.; Malester, B.; Schmidt, S. D.; Thomas-Bryant, T.; Tint, G. S.; Wang, R.; Mercken, M.; Petanceska, S. S.; Duff, K. E.

In: Neurobiology of Disease, Vol. 8, No. 5, 2001, p. 890-899.

Research output: Contribution to journalArticle

Refolo, LM, Pappolla, M, LaFrancois, J, Malester, B, Schmidt, SD, Thomas-Bryant, T, Tint, GS, Wang, R, Mercken, M, Petanceska, SS & Duff, KE 2001, 'A cholesterol-lowering drug reduces β-amyloid pathology in a transgenic mouse model of Alzheimer's disease', Neurobiology of Disease, vol. 8, no. 5, pp. 890-899. https://doi.org/10.1006/nbdi.2001.0422
Refolo, L. M. ; Pappolla, Miguel ; LaFrancois, J. ; Malester, B. ; Schmidt, S. D. ; Thomas-Bryant, T. ; Tint, G. S. ; Wang, R. ; Mercken, M. ; Petanceska, S. S. ; Duff, K. E. / A cholesterol-lowering drug reduces β-amyloid pathology in a transgenic mouse model of Alzheimer's disease. In: Neurobiology of Disease. 2001 ; Vol. 8, No. 5. pp. 890-899.
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