Plasma exchange with albumin replacement for Alzheimer's disease treatment induced changes in serum and cerebrospinal fluid inflammatory mediator levels.

IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Annals of Clinical and Translational Neurology Pub Date : 2024-10-30 DOI:10.1002/acn3.52235
Ricardo Gonzalo, Carla Minguet, Ana María Ortiz, María Isabel Bravo, Oscar L López, Mercè Boada, Agustín Ruiz, Montserrat Costa
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Abstract

Objective: There is extensive literature indicating that inflammatory pathways are affected in Alzheimer's disease (AD). We examined whether plasma exchange with albumin replacement (PE-Alb) can impact the inflammatory status of AD patients and alter the relationship between inflammatory mediators and cognitive measures.

Methods: Serum and cerebrospinal fluid (CSF) samples from 142 AD patients participating in the AMBAR trial (14-month schedule of PE-Alb treatment vs. placebo [sham PE-Alb]) were analyzed for changes from baseline for 19 inflammatory mediators (6 inflammatory cytokines, 9 chemokines, and 4 vascular injury indicators) at representative time points across the AMBAR study (lasting effects) as well as in pre- versus post-PE-Alb procedure (acute effects). Association between mediator changes and clinical outcomes reported in the AMBAR study (cognitive, functional, behavioral function, and global change tests) was assessed.

Results: PE-Alb significantly reduced IFN-γ, eotaxin, MIP-1α and ICAM-1 levels in serum, and eotaxin-3 and MIP-1β levels in CSF, at various time points during treatment (p < 0.05; false discovery rate-corrected). Vascular injury indicators were the mediators mostly affected by post- versus pre-PE-Alb level reduction. Increased serum MIP-1α levels were associated with worsening in ADAS-Cog, CDR-sb, and ADCS-CGIC scores in the placebo group, but not in the PE-Alb-treated group.

Interpretation: Peripheral intervention could affect AD by reducing inflammatory mediators in both peripheral and central compartments. Changes in MIP-1α due to PE-Alb were associated with changes in clinical outcomes.

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用白蛋白替代血浆交换治疗阿尔茨海默病会引起血清和脑脊液炎症介质水平的变化。
目的:大量文献表明,阿尔茨海默病(AD)的炎症通路受到影响。我们研究了血浆置换白蛋白(PE-Alb)是否会影响阿尔茨海默病患者的炎症状态,并改变炎症介质与认知指标之间的关系:分析了142名参与AMBAR试验(14个月的PE-Alb治疗计划与安慰剂[假PE-Alb]对比)的AD患者的血清和脑脊液(CSF)样本,以了解19种炎症介质(6种炎症细胞因子、9种趋化因子和4种血管损伤指标)在AMBAR研究的代表性时间点(持久效应)以及PE-Alb治疗前与治疗后(急性效应)的基线变化。评估了介导因子变化与 AMBAR 研究中报告的临床结果(认知、功能、行为功能和整体变化测试)之间的关联:结果:在治疗过程中的不同时间点,PE-Alb 能明显降低血清中 IFN-γ、共济失调素、MIP-1α 和 ICAM-1 的水平,以及脑脊液中共济失调素-3 和 MIP-1β 的水平(p 解释:PE-Alb 能明显降低血清中 IFN-γ、共济失调素、MIP-1α 和 ICAM-1 的水平:外周干预可通过减少外周和中枢分区的炎症介质来影响 AD。PE-Alb引起的MIP-1α的变化与临床结果的变化有关。
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来源期刊
Annals of Clinical and Translational Neurology
Annals of Clinical and Translational Neurology Medicine-Neurology (clinical)
CiteScore
9.10
自引率
1.90%
发文量
218
审稿时长
8 weeks
期刊介绍: Annals of Clinical and Translational Neurology is a peer-reviewed journal for rapid dissemination of high-quality research related to all areas of neurology. The journal publishes original research and scholarly reviews focused on the mechanisms and treatments of diseases of the nervous system; high-impact topics in neurologic education; and other topics of interest to the clinical neuroscience community.
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