伴有β淀粉样蛋白沉积的痴呆患者血清胆红素/白蛋白浓度异常及静脉输注白蛋白治疗阿尔茨海默病的益处
Abnormal Serum Bilirubin/Albumin Concentrations in Dementia Patients With Aβ Deposition and the Benefit of Intravenous Albumin Infusion for Alzheimer's Disease Treatment.
作者信息
Zhong Xiaomei, Liao Yuning, Chen Xinru, Mai Naikeng, Ouyang Cong, Chen Ben, Zhang Min, Peng Qi, Liang Wanyuan, Zhang Weiru, Wu Zhangying, Huang Xingxiao, Li Caijun, Chen Hong, Lao Weimin, Zhang Chang-E, Wang Xuejun, Ning Yuping, Liu Jinbao
机构信息
Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China.
Protein Modification and Degradation Lab, SKLRD, School of Basic Medical Sciences, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, China.
出版信息
Front Neurosci. 2020 Sep 3;14:859. doi: 10.3389/fnins.2020.00859. eCollection 2020.
BACKGROUND
Our previous study in animal models revealed that bilirubin could induce Aβ formation and deposition. Bilirubin may be important in neurodegenerative dementia with Aβ deposition. Hence, lowering the concentration of the free bilirubin capable of crossing the blood brain-barrier may benefit the treatment of Alzheimer's disease (AD).
OBJECTIVES
The objectives of this study were to examine the change in the serum bilirubin and albumin concentrations of dementia patients with Aβ deposition, and to determine the effects of intravenous administration of albumin in the treatment of AD.
METHODS
Bilirubin and albumin concentrations in dementia patients with Aβ deposition were examined. Cell viability and apoptosis were determined in dopaminergic neuron-like cells MN9D treated with bilirubin in the presence of diverse concentrations of serum. Human albumin at a dose of 10 g every 2 weeks for 24 weeks was administered intravenously to AD patients to examine the effect of albumin on AD symptoms.
RESULTS
Significantly higher indirect bilirubin (IBIL) concentrations, lower albumin concentrations, and higher ratio of IBIL to albumin (IBIL/ALB) were observed in dementia patients with Aβ deposition, including AD, dementia with Lewy bodies, and general paresis of insane. assays showed that bilirubin-induced injury in cultured dopaminergic neuron-like cells negatively depends on the concentration of serum in the culture medium. General linear model with repeated measures analysis indicated a main effect of group on the change in albumin concentrations and Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory scale (ADCS-ADL) scores, and the main effect of time and group, and group-by-time interaction on the change of Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) scores. Analysis of the combined data of the entire 28 weeks of assessment period using the area under curve convincingly showed significantly improvements in the change of albumin concentrations, ADCS-ADL scores, and CDR-SB scores.
CONCLUSION
IBIL and the IBIL/ALB ratio are significantly higher in dementia patients with Aβ deposition, and intravenous administration of albumin is beneficial to AD treatment.
TRIAL REGISTRATION
The intervention study was registered at http://www.chictr.org.cn (ChiCTR-IOR-17011539). Date of registration: June 1, 2017.
背景
我们之前在动物模型中的研究表明，胆红素可诱导β淀粉样蛋白（Aβ）的形成和沉积。胆红素可能在伴有Aβ沉积的神经退行性痴呆中起重要作用。因此，降低能够穿过血脑屏障的游离胆红素浓度可能有助于阿尔茨海默病（AD）的治疗。
目的
本研究旨在检测伴有Aβ沉积的痴呆患者血清胆红素和白蛋白浓度的变化，并确定静脉输注白蛋白治疗AD的效果。
方法
检测伴有Aβ沉积的痴呆患者的胆红素和白蛋白浓度。在不同浓度血清存在的情况下，检测用胆红素处理的多巴胺能神经元样细胞MN9D的细胞活力和凋亡情况。每2周给AD患者静脉注射10 g人白蛋白，共24周，以检测白蛋白对AD症状的影响。
结果
在伴有Aβ沉积的痴呆患者中，包括AD、路易体痴呆和麻痹性痴呆患者，观察到间接胆红素（IBIL）浓度显著升高、白蛋白浓度降低以及IBIL与白蛋白的比值（IBIL/ALB）升高。实验表明，胆红素诱导的培养多巴胺能神经元样细胞损伤与培养基中血清浓度呈负相关。重复测量的一般线性模型分析表明，分组对白蛋白浓度变化和阿尔茨海默病协作研究日常生活活动量表（ADCS-ADL）评分有主要影响，时间和分组对临床痴呆评定量表-方框总和（CDR-SB）评分变化有主要影响，分组与时间的交互作用也有影响。使用曲线下面积对整个28周评估期的合并数据进行分析，令人信服地表明白蛋白浓度、ADCS-ADL评分和CDR-SB评分的变化有显著改善。
结论
伴有Aβ沉积的痴呆患者的IBIL和IBIL/ALB比值显著升高，静脉输注白蛋白对AD治疗有益。
试验注册
干预研究在http://www.chictr.org.cn（中国临床试验注册中心注册号：ChiCTR-IOR-17011539）注册。注册日期：2017年6月1日。
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