Evidence map›Paper›PMID 40045480›Full record

ArticleBrain pathology (Zurich, Switzerland)2025

Sterol imbalances and cholesterol-24-hydroxylase dysregulation is linked to the underlying progression of multiple sclerosis.

Lauren Griffiths, Kristen Hawkins, Eylan Yutuc, Roberto Angelini, Racheal Fosuah, Manuela Pacciarini, Alison Dickson, Neil Robertson, Laura Childs, Samantha Loveless and 4 more

Abstract read
In one paragraph

Article in Brain pathology (Zurich, Switzerland), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Lauren GriffithsInstitute of Life Sciences 1, Faculty of Medicine, Health and Life Sciences, Swansea University, Swansea, UK.ORCID https://orcid.org/0000-0002-8713-3687
Kristen HawkinsInstitute of Life Sciences 1, Faculty of Medicine, Health and Life Sciences, Swansea University, Swansea, UK.
Eylan YutucInstitute of Life Sciences 1, Faculty of Medicine, Health and Life Sciences, Swansea University, Swansea, UK.
Roberto AngeliniInstitute of Life Sciences 1, Faculty of Medicine, Health and Life Sciences, Swansea University, Swansea, UK.
Racheal FosuahInstitute of Life Sciences 1, Faculty of Medicine, Health and Life Sciences, Swansea University, Swansea, UK.
Manuela PacciariniInstitute of Life Sciences 1, Faculty of Medicine, Health and Life Sciences, Swansea University, Swansea, UK.
Alison DicksonInstitute of Life Sciences 1, Faculty of Medicine, Health and Life Sciences, Swansea University, Swansea, UK.
Neil RobertsonDivision of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
Laura ChildsDivision of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
Samantha LovelessDivision of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.ORCID https://orcid.org/0000-0002-5124-4115
Emma TallantyreDivision of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
William J GriffithsInstitute of Life Sciences 1, Faculty of Medicine, Health and Life Sciences, Swansea University, Swansea, UK.
Yuqin WangInstitute of Life Sciences 1, Faculty of Medicine, Health and Life Sciences, Swansea University, Swansea, UK.
Owain W HowellInstitute of Life Sciences 1, Faculty of Medicine, Health and Life Sciences, Swansea University, Swansea, UK.ORCID https://orcid.org/0000-0003-2157-9157

Funding

Biotechnology and Biological Sciences Research Council BB/L001942/1Biotechnology and Biological Sciences Research Council BB/N015932/1Biotechnology and Biological Sciences Research Council BB/S019588/1Biotechnology and Biological Sciences Research Council BB/T018542/1BRAIN Unit Infrastructure Award UA05Medical Research Council Impact Acceleration AccountMultiple Sclerosis Society 94
6 · The paper itself

Abstract

Disability worsening in multiple sclerosis (MS) is linked to neurodegeneration. Cholesterol homeostasis is essential for normal brain function. CYP46A1, crucial for brain cholesterol turnover and reduced in some neurodegenerative diseases, is a potential neuroprotective target. We hypothesized that CYP46A1 is downregulated in MS brains and linked to cholesterol dysbalance. Mass spectrometric analysis of sterols was performed from matched plasma and cerebrospinal fluid (CSF) in an all-female MS cohort (n = 32, mean age = 33). Disability status was recorded at baseline and follow-up. MS brain tissue samples (n = 11; 7 females; ages 38-67; 10 Secondary Progressive MS, 1 Primary Progressive MS; Disease Duration: 13-49 years) and control samples (n = 8; 3 females; ages 41-68) analysed for pathological regions using mass spectrometry and RNA expression using in-situ hybridization. Significant dysregulation in 25-hydroxycholesterol, 27-hydroxycholesterol and 3β-hydroxycholestenoic acid in CSF correlated with disability at baseline and follow-up in the patient population. In brain tissue, reduced cholesterol, 24S-hydroxycholesterol and 24S,25-epoxycholesterol were observed in white matter lesions (p < 0.05), linked to CYP46A1 activity. CYP46A1 expression was enriched in neurons, with reductions in MS grey matter lesions and non-lesions compared to controls (p < 0.01). Cholesterol metabolism is dysregulated in MS and is associated with reduced neuron-specific CYP46A1 expression. Modulating CYP46A1, a druggable target, may benefit progressive MS.

Indexed as

Cholesterol 24-HydroxylaseMultiple SclerosisSteroid HydroxylasesSterolsAdultAgedBrainCholesterolDisease ProgressionFemaleHumansHydroxycholesterolsMiddle AgedCholesterolCholesterol 24-HydroxylaseHydroxycholesterolsSteroid HydroxylasesSterolscholesterolcholesterol‐24‐hydroxylase (CYP46A1)mass spectrometrymultiple sclerosis (MS)neurodegenerationprogressionsterols

Identifiers

PMID40045480
PMCPMC12352928

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.