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Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation
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We have previously demonstrated that the brain contains about 80% of the 24S-hydroxycholesterol in the human body and that there is a net flux of this steroid from the brain into the circulation (Lütjohann, D. et al. 1996. Proc. Natl. Acad. Sci. USA. 93: 9799-9804). Combining previous data with new data on 12 healthy volunteers, the arteriovenous difference between levels of this oxysterol in the internal jugular vein and in a peripheral artery was found to be -10.2 +/- 2.8 ng/ml (mean +/- SEM) corresponding to a net flux of 24S-hydroxycholesterol from the brain of about 6.4 mg/24 h. The arteriovenous difference between levels of 24S-hydroxycholesterol in the hepatic vein and a peripheral artery of 12 other volunteers was found to be 7.4 +/- 2.2 ng/ml, corresponding to a hepatic uptake of about 7.6 mg/24 h. The concentrations of 24S-hydroxycholesterol in the renal vein were about the same as those in a peripheral artery, indicating that a renal elimination is not of importance. Intravenously injected deuterium-labeled racemic 24-hydroxycholesterol was eliminated from the circulation of two human volunteers with half-lives of 10 h and 14 h, respectively. A positive correlation was found between the levels of circulating cholesterol and 24S-hydroxycholesterol. The results are consistent with a cerebral origin of most of the circulating 24S-hydroxycholesterol and suggest that the liver is the major eliminating organ. It is concluded that conversion into 24S-hydroxycholesterol is a quantitatively important mechanism for elimination of cholesterol from human brain. The possibility is discussed that circulating levels of 24S-hydroxycholesterol can be used as a marker for pathological and/or developmental changes in the brain.
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ApoE mediates inter-cellular cholesterol transport from non-neuronal to neuronal cells.
“Extensive studies have established the role of ApoE in mediating inter-cellular cholesterol transport from non-neuronal to neuronal cells (Björkhem et al., 1998; Mauch et al., 2001)”
From ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism (2021) · cites this paper as Björkhem et al., 1998
The “Flux of 24S-hydroxycholesterol from the brain” section discusses an ApoE-dependent mechanism for transporting cholesterol out of the human brain. It does not describe transport from non-neuronal cells to neurons, so the cited paper supports ApoE involvement in cholesterol transport but not the claimed direction between cell types. No page number is available in our copy. (LLM, conf=0.82)
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Metadata
- Authors
- Björkhem, I., Lütjohann, D., Diczfalusy, U., Ståhle, L., Ahlborg, G., & Wahren, J.
- Affiliations
- Karolinska Institutet (SE)
- Karolinska University Hospital (SE)
- Corresponding author
- Björkhem, Ingemar
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 1998-08
- Volume
- 39
- Issue
- 8
- Pages
- 1594-1600
- ISSN
- 0022-2275 (ISSN-L)
- OpenAlex
- W2106009748
- Cited by
- 538
- References
- 1
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 26 · 2023: 24 · 2022: 26 · 2021: 25 · 2020: 19 · 2019: 17 · 2018: 11 · 2017: 9 · 2016: 20 · 2015: 26 · 2014: 21 · 2013: 15 · 2012: 22
- FWCI
- 10.06
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Hjärt-Lungfonden
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Physical Sciences › Chemistry › Organic Chemistry › Steroid Chemistry and Biochemistry
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- 24S-hydroxycholesterol, oxysterols, cholesterol homeostasis, hepatic uptake, arteriovenous differences, elimination half-life, circulating cholesterol
- MeSH terms
- Adult, Brain, Cholesterol, Deuterium, Half-Life, Homeostasis, Humans, Hydroxycholesterols, Kidney, Kinetics, Liver, Male, Reference Values, Splanchnic Circulation, Steroid Hydroxylases, Biomarkers
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