Journal Article

DZNE-2020-03279

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Cerebral and extracerebral cholesterol metabolism and CSF markers of Alzheimer's disease.

Popp, J. ; Meichsner, S. ; Kölsch, H. ; Lewczuk, P. ; Maier, W.DZNE* ; Kornhuber, J. ; Jessen, F.DZNE* ; Lütjohann, D.

2013
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.bcp.2012.12.007

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.

Keyword(s): Aged (MeSH) ; Alzheimer Disease: blood (MeSH) ; Alzheimer Disease: cerebrospinal fluid (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Amyloid: metabolism (MeSH) ; Biomarkers: blood (MeSH) ; Biomarkers: cerebrospinal fluid (MeSH) ; Brain: metabolism (MeSH) ; Case-Control Studies (MeSH) ; Cholesterol: metabolism (MeSH) ; Female (MeSH) ; Humans (MeSH) ; Male (MeSH) ; tau Proteins: metabolism (MeSH) ; Amyloid ; Biomarkers ; tau Proteins ; Cholesterol

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Contributing Institute(s):

1. DZNE before 2020 (Pre 2020)
2. U Clinical Researchers - Bonn (U Clinical Researchers - Bonn)
3. Clinical Alzheimer’s Disease Research (AG Jessen)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2013

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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