Apolipoprotein E ε4-Positive Multiple Sclerosis Patients Develop More Gray-Matter and Whole-Brain Atrophy: a 15-Year Disease History Model Based on a 4-Year Longitudinal Study

Horáková, Dana; Kýr, M.; Havrdová, E.; Doležal, O.; Lelková, P.; Pospíšilová, L.; Bergsland, N.; Dwyer, M. G.; Cox, J. L.; Hussein, S.; Seidl, Z.; Vaněčková, M.; Krásenský, J.; Zivadinov, R.

doi:10.14712/fb2010056060242

Folia Biologica > Archive > 2010, Vol. 56 > Issue 6 > Apolipoprotein E ε4-Positive Multiple…

Fol. Biol. 2010, 56, 242-251

https://doi.org/10.14712/fb2010056060242

Apolipoprotein E ε4-Positive Multiple Sclerosis Patients Develop More Gray-Matter and Whole-Brain Atrophy: a 15-Year Disease History Model Based on a 4-Year Longitudinal Study

Dana Horáková¹, M. Kýr^2,3, E. Havrdová¹, O. Doležal¹, P. Lelková⁴, L. Pospíšilová⁴, N. Bergsland⁵, M. G. Dwyer⁵, J. L. Cox⁵, S. Hussein⁵, Z. Seidl⁶, M. Vaněčková⁶, J. Krásenský⁶, R. Zivadinov⁵

¹Charles University in Prague, First Faculty of Medicine, Department of Neurology and Center of Clinical Neuroscience, Prague, Czech Republic
²Department of Paediatric Oncology, Faculty Hospital Brno, Brno, Czech Republic
³Institute of Biostatistics and Analyses, Faculty of Medicine and Faculty of Sciences, Masaryk University, Brno, Czech Republic
⁴Charles University in Prague, First Faculty of Medicine, Department of Paediatrics, Prague, Czech Republic
⁵Buffalo Neuroimaging Analysis Center, Department of Neurology, SUNY Buffalo, Buffalo, NY, USA
⁶Charles University in Prague, First Faculty of Medicine, Department of Radiology, Prague, Czech Republic

Received June 2010
Accepted July 2010

Multiple sclerosis is a disease with considerable individual variation, and genetic background plays a key role in disease susceptibility and severity. The objective of the study was to evaluate the relationship between apolipoprotein E (APOE) genotype and the evolution of different clinical and MRI parameters. We investigated a group of 150 relapsingremitting patients that completed 4-year follow-up. The mean age was 30.2 years, disease duration 56.8 months, and baseline Expanded Disability Status Scale (EDSS) 1.8. The changes in brain parenchymal volume (BPV), gray matter (GMV), white matter (WMV) and peripheral gray volume (PGMV) were measured by SIENA/X. T2-lesion volume was assessed by semi-automated methods. The mixed-effect model analysis was used to investigate evolution of clinical and MRI parameters in relation to the APOE ε4 genotype considering two different time models: 4-year follow-up and 15-year period from disease onset. We identified 36 APOE ε4-positive patients. Decline of GMV (P = 0.017), and BPV (P = 0.029) were significantly faster in APOE ε4-positive than in APOE ε4-negative patients in the 15-year model. In the 4-year model, a trend for faster decrease of GMV was found in APOE ε4-positive patients (P = 0.067). No differences in other MRI parameters or EDSS were found between the APOE groups. The results of the study suggest that APOE ε4-positive patients experience faster rate of gray matter atrophy.

Keywords

multiple sclerosis, APOE, brain atrophy, gray matter, MRI, mixed-effect model.

Funding

The ASA study was an investigator-initiated study. The genetic part of the study was supported from the Czech Ministry of Health Grant No. 1A8713-5/2005 and from the Czech Ministry of Education (Research Programme MSM 0021620849). MRI acquisition part of the study was supported by Gedeon Richter and Biogen Idec. The MRI analysis part was supported by Biogen Idec.