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

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    57 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)121-131
    Number of pages11
    JournalJournal of Alzheimer's Disease
    Volume16
    Issue number1
    DOIs
    Publication statusPublished - 2009

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