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Research paper
Apolipoproteins are associated with new MRI lesions and deep grey matter atrophy in clinically isolated syndromes
  1. Richard W Browne1,
  2. Bianca Weinstock-Guttman2,
  3. Dana Horakova3,
  4. Robert Zivadinov2,4,
  5. Mary Lou Bodziak1,
  6. Miriam Tamaño-Blanco5,
  7. Darlene Badgett5,
  8. Michaela Tyblova3,
  9. Manuela Vaneckova6,
  10. Zdenek Seidl6,
  11. Jan Krasensky6,
  12. Niels Bergsland4,
  13. Deepa P Ramasamy4,
  14. Jesper Hagemeier4,
  15. Eva Havrdova3,
  16. Murali Ramanathan2,5
  1. 1Department of Biotechnical and Clinical Laboratory Sciences, State University of New York, Buffalo, New York, USA
  2. 2Department of Neurology, State University of New York, Buffalo, New York, USA
  3. 3Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic
  4. 4Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York, Buffalo, New York, USA
  5. 5Department of Pharmaceutical Sciences, State University of New York, Buffalo, New York, USA
  6. 6Department of Radiology, 1st Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic
  1. Correspondence to
    Professor Murali Ramanathan, 355 Kapoor Hall, Department of Pharmaceutical Sciences, State University of New York, Buffalo, Buffalo, NY 14214-8033, USA; Murali{at}Buffalo.Edu

Abstract

Objectives There is increasing evidence that serum lipoprotein cholesterol biomarkers are associated with disease progression in clinically isolated syndromes (CIS). Apolipoproteins (Apo) are recognition ligands that mediate the physiological interactions of cholesterol-containing lipoproteins. The objective of this study was to investigate whether serum Apo levels are associated with CIS disease progression.

Methods ApoB, ApoAI, ApoAII, ApoE and lipoprotein (a) (Lpa) levels were measured in serum samples obtained prior to the start of treatment from 181 CIS patients (123 women, 58 men, 68% women; mean age: 28.1±SD 8.1 years). All patients were treated with intramuscular interferon-β as part of the prospective study. Clinical and MRI assessments were obtained at baseline, 6, 12 and 24 months after start of interferon-β treatment.

Results Greater ApoB levels were associated with increased number of new T2 lesions (p<0.001) and increased number of new or enlarging T2 lesions (p<0.001) over 2 years. Each 10 mg/dL of greater baseline ApoB is associated with a 16% increase in the number of new T2 lesions over 2 years. ApoAI, ApoAII, ApoE and Lpa were not associated with T2 lesions. Greater ApoE levels were associated with greater deep grey matter atrophy (partial correlation rp=−0.28, p<0.001). Each 1 mg/dL increment in ApoE levels was associated with a 1% increase in deep grey matter atrophy over 2 years.

Conclusions Serum ApoB levels are associated with new lesion accumulation whereas ApoE levels are associated with deep grey matter atrophy in high risk CIS patients treated with interferon β-1a.

  • Apolipoproteins
  • Cholesterol
  • Interferon
  • MRI
  • Multiple Sclerosis

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