Impact of 27-hydroxycholesterol on amyloid-β peptide production and ATP-binding cassette transporter expression in primary human neurons

Woojin Scott Kim, Sharon L. Chan, Andrew F. Hill, Gilles J. Guillemin, Brett Garner

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Cholesterol is an integral component of neuronal membranes and recent evidence has shown that it regulates amyloid-β protein precursor processing to form amyloid-β peptides, which are a major constituent of cerebral amyloid plaques associated with Alzheimer's disease. 27-Hydroxycholesterol (27OHC) is synthesized from cholesterol via sterol 27-hydroxylase (CYP27A1) in the brain and, unlike cholesterol, can cross into the brain through the blood brain barrier from the circulation. Previous studies point toward a potential role for 27OHC in the regulation of neuronal amyloid-β peptide generation, however, this has not been investigated in primary human neurons. Here we show that 27OHC significantly reduced amyloid-β peptide detected in cell culture supernatants from primary human neurons. We also show that 27OHC does not affect α-, β- or γ-secretase activity but does upregulate the liver X receptor (LXR) responsive genes ABCA1, ABCG1 and APOE. These data suggest that 27OHC-mediated reduction in extracellular amyloid-β peptide levels is potentially due to its action as an LXR ligand.

LanguageEnglish
Pages121-131
Number of pages11
JournalJournal of Alzheimer's Disease
Volume16
Issue number1
DOIs
Publication statusPublished - 2009

Fingerprint

ATP-Binding Cassette Transporters
Amyloid beta-Peptides
Neurons
Cholesterol
Cholestanetriol 26-Monooxygenase
Amyloid Precursor Protein Secretases
Primary Cell Culture
Amyloid beta-Protein Precursor
Amyloid Plaques
Brain
Blood-Brain Barrier
Alzheimer Disease
Up-Regulation
Ligands
Membranes
27-hydroxycholesterol
Genes
Liver X Receptors

Cite this

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title = "Impact of 27-hydroxycholesterol on amyloid-β peptide production and ATP-binding cassette transporter expression in primary human neurons",
abstract = "Cholesterol is an integral component of neuronal membranes and recent evidence has shown that it regulates amyloid-β protein precursor processing to form amyloid-β peptides, which are a major constituent of cerebral amyloid plaques associated with Alzheimer's disease. 27-Hydroxycholesterol (27OHC) is synthesized from cholesterol via sterol 27-hydroxylase (CYP27A1) in the brain and, unlike cholesterol, can cross into the brain through the blood brain barrier from the circulation. Previous studies point toward a potential role for 27OHC in the regulation of neuronal amyloid-β peptide generation, however, this has not been investigated in primary human neurons. Here we show that 27OHC significantly reduced amyloid-β peptide detected in cell culture supernatants from primary human neurons. We also show that 27OHC does not affect α-, β- or γ-secretase activity but does upregulate the liver X receptor (LXR) responsive genes ABCA1, ABCG1 and APOE. These data suggest that 27OHC-mediated reduction in extracellular amyloid-β peptide levels is potentially due to its action as an LXR ligand.",
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Impact of 27-hydroxycholesterol on amyloid-β peptide production and ATP-binding cassette transporter expression in primary human neurons. / Scott Kim, Woojin; Chan, Sharon L.; Hill, Andrew F.; Guillemin, Gilles J.; Garner, Brett.

In: Journal of Alzheimer's Disease, Vol. 16, No. 1, 2009, p. 121-131.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Scott Kim, Woojin

AU - Chan, Sharon L.

AU - Hill, Andrew F.

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AU - Garner, Brett

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AB - Cholesterol is an integral component of neuronal membranes and recent evidence has shown that it regulates amyloid-β protein precursor processing to form amyloid-β peptides, which are a major constituent of cerebral amyloid plaques associated with Alzheimer's disease. 27-Hydroxycholesterol (27OHC) is synthesized from cholesterol via sterol 27-hydroxylase (CYP27A1) in the brain and, unlike cholesterol, can cross into the brain through the blood brain barrier from the circulation. Previous studies point toward a potential role for 27OHC in the regulation of neuronal amyloid-β peptide generation, however, this has not been investigated in primary human neurons. Here we show that 27OHC significantly reduced amyloid-β peptide detected in cell culture supernatants from primary human neurons. We also show that 27OHC does not affect α-, β- or γ-secretase activity but does upregulate the liver X receptor (LXR) responsive genes ABCA1, ABCG1 and APOE. These data suggest that 27OHC-mediated reduction in extracellular amyloid-β peptide levels is potentially due to its action as an LXR ligand.

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