Karin Maria Thelen

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BACKGROUND Myopathy, probably caused by 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibition in skeletal muscle, rarely occurs in patients taking statins. This study was designed to assess the effect of high-dose statin treatment on cholesterol and ubiquinone metabolism and mitochondrial function in human skeletal muscle. METHODS Forty-eight(More)
On a global scale, there is an increasing tendency for a more aggressive treatment of hypercholesterolemia. Minor effects of statins on brain cholesterol metabolism have been reported in some in vivo animal studies, and it seems that this is due to a local effect of the drug. We treated male mice of the inbred strain C57/BL6 with a high daily dose of(More)
BACKGROUND Glutathione S-transferase omega-1 (GSTO1) protects from oxidative stress, a risk factor for Alzheimer disease (AD), vascular dementia (VaD), and stroke. Polymorphisms in GSTO1 might influence the function of the protein and thus the risk of AD, VaD, and stroke. METHODS The GSTO1 gene was screened for variations. The effect of the detected(More)
Recent epidemiological studies suggest that inhibitors of 3-hydroxy-3-methyl-glutaryl CoA reductase, so-called statins, are effective in lowering the prevalence of Alzheimer's disease. Whether the effect of statins is due to a local inhibition of cholesterol synthesis in the brain or whether it is mediated by the reduced levels of cholesterol in the(More)
During the last three to four decades, interest in the interaction of circulating and brain cholesterol has increased. As the CNS matures and cholesterol pools in the brain become constant, the rate of de novo synthesis of cholesterol in the brain is expected to decline. We measured cholesterol, its precursors and its brain specific metabolite(More)
The cholesterol-synthesizing enzyme seladin-1, encoded by the Dhcr24 gene, is a flavin adenine dinucleotide-dependent oxidoreductase and regulates responses to oncogenic and oxidative stimuli. It has a role in neuroprotection and is downregulated in affected neurons in Alzheimer's disease (AD). Here we show that seladin-1-deficient mouse brains had reduced(More)
Presenilins (PSs) are components of the gamma-secretase complex that mediates intramembranous cleavage of type I membrane proteins. We show that gamma-secretase is involved in the regulation of cellular lipoprotein uptake. Loss of gamma-secretase function decreased endocytosis of low-density lipoprotein (LDL) receptor. The decreased uptake of lipoproteins(More)
Sterol regulatory element binding proteins-1 and -2 (SREBPs) are transcription factors controlling lipid homeostasis in human cells. The G-allele carriers of the SREBF-1 gene C-G polymorphism in exon 18c and coding for glycine at the protein level (G952G) have shown to associate more frequently with obesity and type 2 diabetes than the C-allele carriers.(More)
A large number of studies deals with the association of cholesterol and Abeta levels, however, the results are so far controversial. Whereas some studies report on increased cholesterol levels, other authors refer to an association of decreased peripheral cholesterol and the incidence of Alzheimer's disease. It is also questionable whether plasma(More)
Apolipoprotein E (apoE) is a regulator of peripheral cholesterol homeostasis, and the apoE-isoform E4 is a major risk factor for the development of Alzheimer's disease (AD). Accumulating evidence suggests a key role for aberrant cholesterol metabolism in AD. We hypothesized that apoE-deficiency in mice not only affects cholesterol homeostasis in the(More)