Abstract | BACKGROUND: RESULTS: We determined the effect of 24-OHC and/or 27-OHC on Abeta generation in SH-SY5Y cells. We found that while 27-OHC increases levels of Abeta42, 24-OHC did not affect levels of this peptide. Increased Abeta42 levels with 27-OHC are associated with increased levels of beta-amyloid precursor protein (APP) as well as beta-secretase (BACE1), the enzyme that cleaves APP to yield Abeta. Unchanged Abeta42 levels with 24-OHC are associated with increased levels of sAPPalpha, suggesting that 24-OHC favors the processing of APP to the non-amyloidogenic pathway. Interestingly, 24-OHC, but not 27-OHC, increases levels of the ATP-binding cassette transporters, ABCA1 and ABCG1, which regulate cholesterol transport within and between cells. CONCLUSION: These results suggest that cholesterol metabolites are linked to Abeta42 production. 24-OHC may favor the non-amyloidogenic pathway and 27-OHC may enhance production of Abeta42 by upregulating APP and BACE1. Regulation of 24-OHC: 27-OHC ratio could be an important strategy in controlling Abeta42 levels in AD.
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Authors | Jaya Rp Prasanthi, Amber Huls, Sarah Thomasson, Alex Thompson, Eric Schommer, Othman Ghribi |
Journal | Molecular neurodegeneration
(Mol Neurodegener)
Vol. 4
Pg. 1
(Jan 06 2009)
ISSN: 1750-1326 [Electronic] England |
PMID | 19126211
(Publication Type: Journal Article)
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