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Peer-reviewedCC BY-NC-NDAnnals of clinical and translational neurology

Dysregulated Cholesterol Metabolism, Chronic Inflammation, and Disability in Severe Progressive Multiple Sclerosis.

  • Taylor R Wicks1
  • Mujeeb Shittu2
  • Anna Wolska3
  • Diala Ghazal2
  • Bianca Weinstock-Guttman4
  • Alexander Burnham5
  • Alan T Remaley3
  • Robert Zivadinov6,7
  • Murali Ramanathan1,4
7 affiliations
  1. 1Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, New York, USA.
  2. 2Department of Biotechnical and Clinical Laboratory Sciences, University at Buffalo, The State University of New York, Buffalo, New York, USA.
  3. 3Lipoprotein Metabolism Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
  4. 4Jacobs Multiple Sclerosis Center, Department of Neurology, University at Buffalo, The State University of New York, Buffalo, New York, USA.
  5. 5The Boston Home, Dorchester, Massachusetts, USA.
  6. 6Buffalo Neuroimaging Analysis Center, Department of Neurology, University at Buffalo, The State University of New York, Buffalo, New York, USA.
  7. 7Center for Biomedical Imaging, University at Buffalo, State University of New York, Buffalo, New York, USA.
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Abstract

Background

Dysregulated lipid metabolism, which can affect remyelination and neural repair, has not been extensively investigated in progressive multiple sclerosis (PMS). The goal was to examine whether dysregulated cholesterol metabolism was associated with disability in PMS.Methods

The study sample comprised 53 Severe PMS patients (Expanded Disability Status Scale, EDSS score: 7.0-9.5) requiring skilled nursing and 53 age, sex- and disease duration-matched community-dwelling Control PMS patients (EDSS score: 3.0-6.5). Patients underwent neurological examinations and provided blood samples. Cholesterol and apolipoprotein (Apo) profiles, nuclear magnetic resonance spectroscopy metabolomic profiles, inflammatory cytokines, neuroaxonal, and glial injury biomarkers were obtained. Disability was measured on the EDSS and the Combinatorial Weight-Adjusted Disability (CombiWISE) scales.Results

The Severe PMS group had lower high-density lipoprotein cholesterol (HDL-C), ApoA-I, and ApoA-II levels (all p < 0.001) and higher ApoB and ApoE levels. The nutritional status biomarker, albumin, was lower, and the chronic inflammation marker, GlycA, was higher in Severe PMS versus Control PMS (all p < 0.001). Total cholesterol, ApoA-II, and ApoB were associated with disability on the EDSS and CombiWISE scale. Difference-correlogram analyses revealed substantial remodeling of biomarker interdependencies in Severe PMS. ApoE showed stronger associations with lipid and nutritional biomarkers in Severe PMS, but with neuroaxonal markers (serum neurofilament light chain, glial fibrillary acidic protein) in Control PMS. Inflammatory cytokines (tumor necrosis factor, interleukin-6) showed stronger associations with apolipoproteins in Severe PMS, whereas several lipid-inflammation and lipid nutritional correlations were attenuated.Conclusions

Disrupted cholesterol metabolism and chronic inflammation are strongly linked to greater disability in Severe PMS. Our results also indicate marked alterations in metabolic, inflammatory, nutritional, and neuroglial biomarker networks in Severe PMS.

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Cite

BibTeXRIS
BibTeX
@article{wicks2026dysregulated,
  title = {{Dysregulated Cholesterol Metabolism, Chronic Inflammation, and Disability in Severe Progressive Multiple Sclerosis.}},
  author = {Taylor R Wicks and Mujeeb Shittu and Anna Wolska and Diala Ghazal and Bianca Weinstock-Guttman and Alexander Burnham and Alan T Remaley and Robert Zivadinov and Murali Ramanathan},
  journal = {Annals of clinical and translational neurology},
  year = {2026},
  month = oct,
  doi = {10.1002/acn3.70550},
  url = {https://europepmc.org/article/MED/42885107},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Dysregulated Cholesterol Metabolism, Chronic Inflammation, and Disability in Severe Progressive Multiple Sclerosis.
AU  - Taylor R Wicks
AU  - Mujeeb Shittu
AU  - Anna Wolska
AU  - Diala Ghazal
AU  - Bianca Weinstock-Guttman
AU  - Alexander Burnham
AU  - Alan T Remaley
AU  - Robert Zivadinov
AU  - Murali Ramanathan
PY  - 2026
DA  - 2026/10/15
JO  - Annals of clinical and translational neurology
DO  - 10.1002/acn3.70550
UR  - https://europepmc.org/article/MED/42885107
AB  - Background  Dysregulated lipid metabolism, which can affect remyelination and neural repair, has not been extensively investigated in progressive multiple sclerosis (PMS). The goal was to examine whether dysregulated cholesterol metabolism was associated with disability in PMS.Methods  The study sample comprised 53 Severe PMS patients (Expanded Disability Status Scale, EDSS score: 7.0-9.5) requiring skilled nursing and 53 age, sex- and disease duration-matched community-dwelling Control PMS patients (EDSS score: 3.0-6.5). Patients underwent neurological examinations and provided blood samples. Cholesterol and apolipoprotein (Apo) profiles, nuclear magnetic resonance spectroscopy metabolomic profiles, inflammatory cytokines, neuroaxonal, and glial injury biomarkers were obtained. Disability was measured on the EDSS and the Combinatorial Weight-Adjusted Disability (CombiWISE) scales.Results  The Severe PMS group had lower high-density lipoprotein cholesterol (HDL-C), ApoA-I, and ApoA-II levels (all p < 0.001) and higher ApoB and ApoE levels. The nutritional status biomarker, albumin, was lower, and the chronic inflammation marker, GlycA, was higher in Severe PMS versus Control PMS (all p < 0.001). Total cholesterol, ApoA-II, and ApoB were associated with disability on the EDSS and CombiWISE scale. Difference-correlogram analyses revealed substantial remodeling of biomarker interdependencies in Severe PMS. ApoE showed stronger associations with lipid and nutritional biomarkers in Severe PMS, but with neuroaxonal markers (serum neurofilament light chain, glial fibrillary acidic protein) in Control PMS. Inflammatory cytokines (tumor necrosis factor, interleukin-6) showed stronger associations with apolipoproteins in Severe PMS, whereas several lipid-inflammation and lipid nutritional correlations were attenuated.Conclusions  Disrupted cholesterol metabolism and chronic inflammation are strongly linked to greater disability in Severe PMS. Our results also indicate marked alterations in metabolic, inflammatory, nutritional, and neuroglial biomarker networks in Severe PMS.
SN  - 2328-9503
ER  -