Are the CSF levels of 24S-hydroxycholesterol a sensitive biomarker for mild cognitive impairment?

Leoni, Valerio; Shafaati, Marjan; Salomon, Alina; Kivipelto, Miia; Björkhem, Ingemar; Wahlund, Lars Olof

doi:10.1016/j.neulet.2005.11.046

Cited by 76 publications

(78 citation statements)

References 25 publications

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“…In a follow-up study, also involving German patients, Schönknecht et al demonstrated a significant increase in CSF 24S-hydroxycholesterol from AD patients (2.6 ± 1.1 ng/mL, n = 14) than controls (1.6 ± 0.6 ng/mL, n = 10), but again differences in plasma CSF levels were not significantly different (AD 60.5 ± 19.3 ng/mL; control 53.6 ± 14.3 ng/mL) [52]. In a further study, this time with a Swedish cohort, Leoni [53]. Over all, these three studies agree that CSF 24S-hydroxycholesterol is elevated in CSF from AD patients, this is explained by neuronal damage or demyelination causing an increase in cholesterol which is subsequently metabolised by neuron specific CYP46A1 to 24S-hydroxycholesterol.…”

Section: Neurosterols and Neurodegenerative Diseasementioning

confidence: 80%

“…The levels of oxysterols in human CSF have been studied in detail by Lütjohann's group in Bonn and Björkhem and colleagues in Stockholm [39,[50][51][52][53]. Both groups have used the methodology developed by Dzeletovic et al for plasma analysis (described above in Section 2) with minor modifications [9].…”

Section: Csfmentioning

confidence: 99%

“…It is perhaps also note worthy that levels of 27-hydroxycholesterol in CSF were also found to be significantly elevated in patients with MCI (1. 8 [53] as patients with AD may have BBB or blood-CSF dysfunction [54].…”

Section: Neurosterols and Neurodegenerative Diseasementioning

confidence: 99%

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Analysis of neurosterols by GC–MS and LC–MS/MS

Griffiths

Wang

2009

Journal of Chromatography B

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Section: Neurosterols and Neurodegenerative Diseasementioning

confidence: 80%

Section: Csfmentioning

confidence: 99%

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Analysis of neurosterols by GC–MS and LC–MS/MS

Griffiths

Wang

2009

Journal of Chromatography B

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“…Levels of the tau protein, phosphorylated tau, and b-amyloid in cerebrospinal fluid are routinely used as biomarkers for neurodegenerative diseases and dementia. We recently showed that the level of 24S-hydroxycholesterol in cerebrospinal fluid appears to have about the same diagnostic sensitivity as these markers in connection with Alzheimer's disease and may be the most sensitive marker in early stages [39].…”

Section: S-hydroxycholesterol As a Marker For Neurological And Neurmentioning

confidence: 99%

Rediscovery of Cerebrosterol

Björkhem

2007

Lipids

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24S-hydroxycholesterol was identified more than half a century ago and was initially given the name "cerebrosterol" due to the fact that it was abundant in the brain. A decade ago, we showed that the most important mechanism by which cholesterol is eliminated from the mammalian brain involves a hydroxylation into cerebrosterol followed by diffusion of this steroid over the blood-brain barrier. Using an (18)O(2) inhalation technique, we showed that about two-thirds of the cholesterol synthesis in rat brain is balanced by conversion into cerebrosterol. The hydroxylase responsible for the reaction was found to be dependent upon NADPH and oxygen, consistent with involvement of a species of cytochrome, P-450. The gene coding for the cytochrome P-450 responsible for the reaction was later cloned by the group of David Russell in Dallas and the enzyme was found to be located to neuronal cells in the brain. Recent studies by us and others on this new pathway for elimination of cholesterol from the brain have given new insights into the mechanisms by which cholesterol homeostasis is maintained in this organ. In addition, these studies have resulted in new diagnostic and prognostic tools in connection with neurological and neurodegenerative diseases. An overview of the studies is presented here and the possibility is discussed that the cholesterol 24S-hydroxylase in the brain may be a new drug target in connection with neurodegenerative diseases.

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“…It has been 56,87,148,150,152,156,183,185,188) -114) À -150) À À IsoFs À À À À À HETE m 268) À À m 53) À 7-OHCh À À À À À 7-ketocholesterol À À À À À 24-hydroxycholesterol m 126,171,208,217) À À À À …”

Section: Parkinson's Diseaseunclassified