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@ARTICLE{Popp:136957,
author = {Popp, Julius and Meichsner, Sabrina and Kölsch, Heike and
Lewczuk, Piotr and Maier, Wolfgang and Kornhuber, Johannes
and Jessen, Frank and Lütjohann, Dieter},
title = {{C}erebral and extracerebral cholesterol metabolism and
{CSF} markers of {A}lzheimer's disease.},
journal = {Biochemical pharmacology},
volume = {86},
number = {1},
issn = {0006-2952},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {DZNE-2020-03279},
pages = {37-42},
year = {2013},
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 / Alzheimer Disease: metabolism /
Amyloid: metabolism / Biomarkers: blood / Biomarkers:
cerebrospinal fluid / Brain: metabolism / Case-Control
Studies / Cholesterol: metabolism / Female / Humans / Male /
tau Proteins: metabolism / Amyloid (NLM Chemicals) /
Biomarkers (NLM Chemicals) / tau Proteins (NLM Chemicals) /
Cholesterol (NLM Chemicals)},
cin = {Pre 2020 / U Clinical Researchers - Bonn / AG Jessen},
ddc = {610},
cid = {I:(DE-2719)999999 / I:(DE-2719)7000001 /
I:(DE-2719)1011102},
pnm = {344 - Clinical and Health Care Research (POF3-344)},
pid = {G:(DE-HGF)POF3-344},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:23291240},
doi = {10.1016/j.bcp.2012.12.007},
url = {https://pub.dzne.de/record/136957},
}