Cholesterol metabolism is associated with soluble amyloid precursor protein production in Alzheimer's disease
© 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry.
|Published in:||Journal of neurochemistry, Vol. 123, No. 2 (2012), p. 310-6|
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|Item Description:||Date Completed 11.12.2012|
Date Revised 25.11.2016
Citation Status MEDLINE
Copyright: From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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- © 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry.
- Disturbances of the cholesterol metabolism are associated with Alzheimer's disease (AD) risk and related cerebral pathology. Experimental studies found changing levels of cholesterol and its metabolites 24S-hydroxycholesterol (24S-OHC) and 27-hydroxycholesterol (27-OHC) to contribute to amyloidogenesis by increasing the production of soluble amyloid precursor protein (sAPP). The aim of this study was to evaluate the relationship between the CSF and circulating cholesterol 24S-OHC and 27-OHC, and the sAPP production as measured by CSF concentrations of sAPP forms in humans. The plasma and the CSF concentrations of cholesterol, 24S-OHC and 27-OHC, and the CSF concentrations of sAPPα, sAPPβ, and Aß1-42 were assessed in subjects with AD and controls with normal cognition. In multivariate regression tests including age, gender, albumin ratio, and apolipoprotein E (APOE)ε4 status CSF cholesterol, 24S-OHC, and 27-OHC independently predicted the concentrations of sAPPα and sAPPβ. The associations remained significant when analyses were separately performed in the AD group. Furthermore, plasma 27-OHC concentrations were associated with the CSF sAPP levels. The results suggest that high CSF concentrations of cholesterol, 24S-OHC, and 27-OHC are associated with increased production of both sAPP forms in AD