Departments of Pharmaceutical Sciences, State University of New York, Buffalo, NY, USA.
Biotechnical and Clinical Laboratory Sciences, State University of New York, Buffalo, NY, USA.
Eur J Neurol. 2020 Jan;27(1):188-e4. doi: 10.1111/ene.14055. Epub 2019 Aug 19.
Cholesterol is an important structural component of myelin and essential for brain homeostasis. Our objective was to investigate whether longitudinal changes in cholesterol biomarkers are associated with neurodegeneration in multiple sclerosis (MS).
This prospective, longitudinal study (n = 154) included 41 healthy controls, 76 relapsing-remitting MS subjects and 37 progressive MS subjects. Neurological examination, brain magnetic resonance imaging and blood samples were obtained at baseline and at 5-year follow-up visits. Cholesterol biomarkers measured included plasma total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol and the apolipoproteins ApoA-I, Apo-II, ApoB, ApoC-II and ApoE. Key cholesterol pathway single nucleotide polymorphisms were genotyped.
Greater percentage increases in HDL-C and ApoA-I levels were associated with a lower rate of gray matter and cortical volume loss. Greater percentage increases in low-density lipoprotein cholesterol were associated with increases in new T2 lesions. The percentage increases in HDL-C (P = 0.032) and ApoA-I (P = 0.007) were smaller in patients with relapsing-remitting MS at baseline who converted to secondary progressive MS during the 5-year follow-up period. Changes in HDL-C and ApoA-I were associated with lipoprotein lipase rs328 genotype status.
Increases in HDL-C and ApoA-I have protective associations with magnetic resonance imaging measures of neurodegeneration in MS.
胆固醇是髓鞘的重要结构成分，对大脑内环境稳态至关重要。我们的目的是研究胆固醇生物标志物的纵向变化是否与多发性硬化症（MS）中的神经退行性变有关。
这项前瞻性、纵向研究（n=154）纳入了 41 名健康对照者、76 名复发缓解型 MS 患者和 37 名进展型 MS 患者。在基线和 5 年随访时进行了神经系统检查、脑磁共振成像和血液样本采集。测量的胆固醇生物标志物包括血浆总胆固醇、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇以及载脂蛋白 ApoA-I、Apo-II、ApoB、ApoC-II 和 ApoE。对关键胆固醇途径的单核苷酸多态性进行了基因分型。
HDL-C 和 ApoA-I 水平的百分比增加与灰质和皮质体积损失的速度降低相关。低密度脂蛋白胆固醇的百分比增加与新 T2 病变的增加相关。在基线时患有复发缓解型 MS 且在 5 年随访期间转为继发进展型 MS 的患者中，HDL-C（P=0.032）和 ApoA-I（P=0.007）的百分比增加较小。HDL-C 和 ApoA-I 的变化与脂蛋白脂肪酶 rs328 基因型状态相关。
HDL-C 和 ApoA-I 的增加与 MS 的磁共振成像神经退行性变测量指标具有保护相关性。
