title: Cholesterol metabolism is associated with soluble amyloid precursor protein production in Alzheimer's disease.
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.
authors: Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland. julius.popp@chuv.ch
authors: Julius
authors: J
authors: Popp
authors: Piotr
authors: P
authors: Lewczuk
authors: Heike
authors: H
authors: Kölsch
authors: Sabrina
authors: S
authors: Meichsner
authors: Wolfgang
authors: W
authors: Maier
authors: Johannes
authors: J
authors: Kornhuber
authors: Frank
authors: F
authors: Jessen
authors: Dieter
authors: D
authors: Lütjohann
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis*; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D002784:Cholesterol / Q000378:metabolism*; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015854:Up-Regulation / Q000502:physiology
chemical_list: D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D006888:Hydroxycholesterols; C044563:24-hydroxycholesterol; C076996:27-hydroxycholesterol; D002784:Cholesterol