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24S-hydroxycholesterol in cerebrospinal fluid is elevated in early stages of dementia
Papassotiropoulos A, Lütjohann D, Bagli M, Locatelli S, Jessen F, Buschfort R, Ptok U, Björkhem I et al.. Journal of psychiatric research, 2002-01-01
Topic: Brain proteins, microglia and lab models
The brain is the most cholesterol-rich organ in the human body. Accumulation of excess cholesterol in hippocampal neurons promotes the cleavage of the amyloid precursor protein (APP) into amyloidogenic components with the consequence of the acceleration of neuronal degeneration. Conversion of cholesterol to 24S-hydroxycholesterol mediated by cholesterol 24S-hydroxylase (CYP46) is the major pathway for the elimination of brain cholesterol and the maintenance of brain cholesterol homeostasis. We examined whether cerebrospinal fluid (CSF) 24S-hydroxycholesterol levels differ between patients with dementia, patients with mild cognitive impairment (MCI), and cognitively intact control subjects. Plasma and CSF concentrations of 24S-hydroxycholesterol and cholesterol in 32 patients with Alzheimer's disease (AD), 11 patients with vascular dementia, seven patients with MCI, and seven cognitively intact control subjects were measured by combined gas-chromatography/mass spectrometry. We show elevated concentrations of 24S-hydroxycholesterol in the CSF of AD patients and we interpret this finding as a consequence of increased cholesterol turnover in the central nervous system during neurodegeneration. The observed influence of the apolipoprotein E epsilon4 (APOE4) allele on CSF 24S-hydroxycholesterol concentrations with a gene-dosage effect suggests the existence of a link between the AD risk factor APOE4 and CNS cholesterol metabolism. The elevation of CSF 24S-hydroxycholesterol appears to occur early in the disease process, since patients with mild cognitive impairment had also increased CSF concentrations of this compound. We believe that the CSF concentration of 24S-hydroxycholesterol is altered in AD-related neurodegeneration and thus, CSF 24S-hydroxycholesterol may be a marker for monitoring the onset and progression of the disease.
Key findings
- Plasma and CSF concentrations of 24S-hydroxycholesterol and cholesterol in 32 patients with Alzheimer's disease (AD), 11 patients with vascular dementia, seven patients with MCI, and seven cognitively intact control subjects were measured by combined gas-chromatography/mass spectrometry.
- We show elevated concentrations of 24S-hydroxycholesterol in the CSF of AD patients and we interpret this finding as a consequence of increased cholesterol turnover in the central nervous system during neurodegeneration.
- The observed influence of the apolipoprotein E epsilon4 (APOE4) allele on CSF 24S-hydroxycholesterol concentrations with a gene-dosage effect suggests the existence of a link between the AD risk factor APOE4 and CNS cholesterol metabolism.
- The elevation of CSF 24S-hydroxycholesterol appears to occur early in the disease process, since patients with mild cognitive impairment had also increased CSF concentrations of this compound.
- We believe that the CSF concentration of 24S-hydroxycholesterol is altered in AD-related neurodegeneration and thus, CSF 24S-hydroxycholesterol may be a marker for monitoring the onset and progression of the disease.
Why it matters
This small study found elevated levels of 24S-hydroxycholesterol in the cerebrospinal fluid of people with Alzheimer's disease, which the authors interpret as increased cholesterol turnover in the brain during neurodegeneration. It is a small measurement study and does not test any treatment, cure, or prevention.
Study details
- Participants32
- Evidence strengthLow
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of psychiatric research) |
| Journal's citation record | 2 / 4 | Journal of Psychiatric Research: journal h-index 220 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2002 — older than 20 years, still counted |
| Sample size | 1 / 4 | 32 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 231 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.9 citations a year over 26 year(s) since 2002 |
| Impact for its field and year | 4 / 6 | Cited 8.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 10 other studies in this library |
| Still being cited | 1 / 4 | Cited 13 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Reinhard Heun: h-index 62 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Karolinska Institutet: institution h-index 1,477 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 11755458) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Papassotiropoulos, A., Lütjohann, D., Bagli, M., Locatelli, S., Jessen, F., Buschfort, R., et al. (2002). 24S-hydroxycholesterol in cerebrospinal fluid is elevated in early stages of dementia. Journal of psychiatric research. https://doi.org/10.1016/s0022-3956(01)00050-4
Vancouver
Papassotiropoulos A, Lütjohann D, Bagli M, Locatelli S, Jessen F, Buschfort R, et al. 24S-hydroxycholesterol in cerebrospinal fluid is elevated in early stages of dementia. Journal of psychiatric research. 2002. doi:10.1016/s0022-3956(01)00050-4. PMID: 11755458.
BibTeX
@article{papassotiropoulos2002-11755458,
author = {Papassotiropoulos, A. and Lütjohann, D. and Bagli, M. and Locatelli, S. and Jessen, F. and Buschfort, R. and Ptok, U. and Björkhem, I. and others},
title = {{24S-hydroxycholesterol in cerebrospinal fluid is elevated in early stages of dementia}},
journal = {Journal of psychiatric research},
year = {2002},
doi = {10.1016/s0022-3956(01)00050-4},
pmid = {11755458},
url = {https://doi.org/10.1016/s0022-3956(01)00050-4}
}
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