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- Title
Cholesterol metabolism is associated with soluble amyloid precursor protein production in Alzheimer's disease.
- Authors
Popp, Julius; Lewczuk, Piotr; Kölsch, Heike; Meichsner, Sabrina; Maier, Wolfgang; Kornhuber, Johannes; Jessen, Frank; Lütjohann, Dieter
- Abstract
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.
- Subjects
CHOLESTEROL metabolism; AMYLOID beta-protein precursor; ALZHEIMER'S disease; HYDROXYCHOLESTEROLS; BLOOD plasma; CEREBROSPINAL fluid
- Publication
Journal of Neurochemistry, 2012, Vol 123, Issue 2, p310
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2012.07893.x