Send to

Choose Destination
J Alzheimers Dis. 2009;16(1):121-31. doi: 10.3233/JAD-2009-0944.

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

Author information

Prince of Wales Medical Research Institute, Randwick, NSW, Australia.


Cholesterol is an integral component of neuronal membranes and recent evidence has shown that it regulates amyloid-beta protein precursor processing to form amyloid-beta 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-beta peptide generation, however, this has not been investigated in primary human neurons. Here we show that 27OHC significantly reduced amyloid-beta peptide detected in cell culture supernatants from primary human neurons. We also show that 27OHC does not affect alpha-, beta- or gamma-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-beta peptide levels is potentially due to its action as an LXR ligand.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for IOS Press
Loading ...
Support Center