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Profile of cholesterol-related sterols in aged amyloid precursor protein transgenic mouse brain
Open accessAbstract
Cholesterol is implicated to play a role in Alzheimer disease pathology. Therefore, the concentrations of cholesterol, its precursors, and its degradation products in brain homogenates of aging wild-type and beta-amyloid precursor protein transgenic mice carrying the Swedish mutation (APP23) were analyzed. Among the sterols measured, lanosterol is the first common intermediate of two different pathways, which use either desmosterol or lathosterol as the predominant precursors for de novo synthesis of brain cholesterol. In young mice, cholesterol is mainly synthesized via the desmosterol pathway, while in aged mice, lathosterol is the major precursor. 24S-hydroxycholesterol (cerebrosterol), which plays a key role in the removal of cholesterol from the brain, modestly increased during aging. No differences in the levels of cholesterol, its precursors, or its metabolites were found between wild-type and APP23 transgenic mice. Moreover, the levels of the exogenous plant sterols campesterol and sitosterol were significantly elevated in the brains of APP23 animals at age 12 and 18 months. This time point coincides with abundant plaque formation.
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“The gas chromatographic method used for cholesterol quantitation was sensitive enough to accurately determine the concentration of desmosterol (only at 7 and 14 days after birth), but not of other cholesterol precursors such as lanosterol, the detection of which at any age requires methods employing gas chromatography-mass spectrometry (Lütjohann et al., 2002).”
From Suppression of brain cholesterol synthesis in male Mecp2-deficient mice is age dependent and not accompanied by a concurrent change in the rate of fatty acid synthesis (2017) · cites this paper as Lütjohann et al., 2002
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“These three non-cholesterol sterols have been detected in the brains of mice over a wide age range (Lütjohann et al., 2002).”
From Suppression of brain cholesterol synthesis in male Mecp2-deficient mice is age dependent and not accompanied by a concurrent change in the rate of fatty acid synthesis (2017) · cites this paper as Lütjohann et al., 2002
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Metadata
- Authors
- Lütjohann, D., Brzezinka, A., Barth, E., Abramowski, D., Staufenbiel, M., von Bergmann, K., Beyreuther, K., Multhaup, G., & Bayer, T. A.
- Affiliations
- University of Bonn (DE)
- Novartis (Switzerland) (CH)
- Heidelberg University (DE)
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2002-07
- Volume
- 43
- Issue
- 7
- Pages
- 1078-1085
- ISSN
- 0022-2275 (ISSN-L)
- OpenAlex
- W1975478041
- Cited by
- 158
- References
- 59
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 6 · 2022: 1 · 2021: 3 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 7 · 2016: 10 · 2015: 7 · 2014: 6 · 2013: 9 · 2012: 8
- FWCI
- 6.36
- 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)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- cholesterol, sterols, amyloid precursor protein, APP23 transgenic mice, Alzheimer's disease, brain aging, lanosterol, desmosterol, lathosterol, 24S-hydroxycholesterol, campesterol, sitosterol, phytosterols, amyloid plaques, cholesterol biosynthesis
- MeSH terms
- Aging, Alzheimer Disease, Animals, Blood-Brain Barrier, Brain Chemistry, Cholesterol, Disease Models, Animal, Humans, Mice, Transgenic, Mutation, Phytosterols, Sterols, Blotting, Western, Molecular Structure, Amyloid beta-Protein Precursor, Transgenes, Mice
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