Cerebral and extracerebral cholesterol metabolism and CSF markers of Alzheimer's disease.

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State: Public
Version: author
Serval ID
serval:BIB_A54FC197196A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cerebral and extracerebral cholesterol metabolism and CSF markers of Alzheimer's disease.
Journal
Biochemical Pharmacology
Author(s)
Popp J., Meichsner S., Kölsch H., Lewczuk P., Maier W., Kornhuber J., Jessen F., Lütjohann D.
ISSN
1873-2968 (Electronic)
ISSN-L
0006-2952
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
86
Number
1
Pages
37-42
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
The disturbances of the cholesterol synthesis and metabolism described in Alzheimer's disease (AD) may be both a consequence of the neurodegenerative process and a contributor to the pathogenesis. These putative relationships and their underlying mechanisms are not well understood. The aim of this study was to evaluate the relationship between the cerebral and extracerebral cholesterol synthesis and metabolism, and the AD pathology as reflected by CSF markers in humans. We evaluated the relationships between the plasma and the cerebrospinal fluid (CSF) concentrations of cholesterol, the cholesterol precursors lanosterol, lathosterol and desmosterol, and the cholesterol elimination products 24S-hydroxycholesterol and 27-hydroxycholesterol, and the CSF markers for AD pathology Aβ1-42 and p-tau181 in 86 subjects with normal cognition and in 107 AD patients. CSF desmosterol, cholesterol and 24S-hydroxycholesterol in the AD group, and CSF 24S-hydroxycholesterol in the control group correlated with the p-tau181 levels. Neither CSF nor plasma concentrations of the included compounds correlated with the CSF Aβ1-42 levels. In multivariate regression tests including age, gender, albumin ratio, number of the APOEε4 alleles, and diagnosis, p-tau181 levels independently predicted the CSF desmosterol, cholesterol and 24S-hydroxycholesterol concentrations. The associations remained significant for CSF cholesterol and 24S-hydroxycholesterol when analyses were separately performed in the AD group. The results suggest that alterations of CNS cholesterol de novo genesis and metabolism are related to neurodegeneration and in particular to the cerebral accumulation of phosphorylated tau.
Keywords
Aged, Alzheimer Disease/blood, Alzheimer Disease/cerebrospinal fluid, Amyloid/metabolism, Biological Markers/blood, Biological Markers/cerebrospinal fluid, Brain/metabolism, Case-Control Studies, Cholesterol/metabolism, Female, Humans, Male, tau Proteins/metabolism
Pubmed
Web of science
Create date
11/08/2013 9:38
Last modification date
20/08/2019 16:10
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