Bandaru Veera Venkata Ratnam, Haughey Norman J
Department of Neurology, Richard T. Johnson Division of Neuroimmunology and Neurological Infections, The Johns Hopkins University School of Medicine, Carnegie 616A, 600 North Wolfe Street, Baltimore, 21287, MD, USA.
Department of Psychiatry, Division of Geriatric Psychiatry and Neuropsychiatry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
BMC Neurosci. 2014 Dec 24;15:137. doi: 10.1186/s12868-014-0137-z.
Cholesterol metabolism is important for the maintenance of myelin and neuronal membranes in the central nervous system. Blood concentrations of the brain specific cholesterol metabolite 24S-hydroxysterol to the peripheral metabolite 27-hydroxycholesterol may be useful surrogate markers for neurodegenerative diseases including Alzheimer's disease, Huntington's disease, HIV-Associated Neurocognitive Disorders, and Multiple Sclerosis. However, current methods to isolate hydroxycholesterols are labor intensive, prone to produce variable extraction efficiencies and do not discriminate between free and esterfied forms of hydroxycholesterols. Since free hydroxycholesterols are the biologically active form of these sterols, separating free from esterfied forms may provide a sensitive measure to identify disease-associated differences in brain sterol metabolism.
We found that average human serum concentrations were 12.3 ± 4.79 ng/ml for free 24(s)-hydroxycholesterol and 17.7 ± 8.5 ng/ml for 27-hydroxycholesterol.
Serum measurements of these biologically active oxysterols may be useful surrogate measures for brain health in a variety of neurodegenerative conditions.
胆固醇代谢对于维持中枢神经系统中的髓磷脂和神经元膜很重要。大脑特异性胆固醇代谢物24S-羟基胆固醇与外周代谢物27-羟基胆固醇的血液浓度可能是包括阿尔茨海默病、亨廷顿舞蹈病、HIV相关神经认知障碍和多发性硬化症在内的神经退行性疾病的有用替代标志物。然而，目前分离羟基胆固醇的方法劳动强度大，容易产生可变的提取效率，并且不能区分游离和酯化形式的羟基胆固醇。由于游离羟基胆固醇是这些固醇的生物活性形式，将游离形式与酯化形式分离可能为识别大脑固醇代谢中与疾病相关的差异提供一种灵敏的方法。
我们发现，游离24(S)-羟基胆固醇的平均人血清浓度为12.3±4.79 ng/ml，27-羟基胆固醇的平均人血清浓度为17.7±8.5 ng/ml。
这些生物活性氧化固醇的血清测量值可能是多种神经退行性疾病中大脑健康的有用替代指标。
