Gonzalo Ricardo, Minguet Carla, Ortiz Ana María, Bravo María Isabel, López Oscar L, Boada Mercè, Ruiz Agustín, Costa Montserrat
Grifols Scientific Innovation Office, Avinguda de la Generalitat 152-158, Sant Cugat del Vallès, 08174, Barcelona, Spain.
Departments of Neurology and Psychiatry, University of Pittsburgh School of Medicine, 811 Kaufmann Medical Building, 3471 Fifth Avenue, Pittsburgh, 15213, Pennsylvania, USA.
Ann Clin Transl Neurol. 2024 Dec;11(12):3280-3291. doi: 10.1002/acn3.52235. Epub 2024 Oct 30.
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.
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.
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.
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.
有大量文献表明，阿尔茨海默病（AD）患者的炎症通路会受到影响。我们研究了白蛋白置换血浆置换（PE-Alb）是否会影响AD患者的炎症状态，并改变炎症介质与认知指标之间的关系。
对参与AMBAR试验的142例AD患者（PE-Alb治疗与安慰剂[假PE-Alb]的14个月治疗方案）的血清和脑脊液（CSF）样本进行分析，以确定在AMBAR研究的代表性时间点（长期效应）以及PE-Alb治疗前后（急性效应）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）相对于基线的变化。评估了AMBAR研究中报告的介质变化与临床结局（认知、功能、行为功能和整体变化测试）之间的关联。
在治疗期间的不同时间点，PE-Alb显著降低了血清中的干扰素-γ、嗜酸性粒细胞趋化因子、巨噬细胞炎性蛋白-1α和细胞间黏附分子-1水平，以及脑脊液中的嗜酸性粒细胞趋化因子-3和巨噬细胞炎性蛋白-1β水平（p < 0.05；经错误发现率校正）。血管损伤指标是受PE-Alb治疗后与治疗前水平降低影响最大的介质。在安慰剂组中，血清巨噬细胞炎性蛋白-1α水平升高与阿尔茨海默病协作研究认知量表（ADAS-Cog）、临床痴呆评定量表总和（CDR-sb）和阿尔茨海默病协作研究日常生活能力量表（ADCS-CGIC）评分恶化相关，但在PE-Alb治疗组中并非如此。
外周干预可通过减少外周和中枢区域的炎症介质来影响AD。PE-Alb导致的巨噬细胞炎性蛋白-1α变化与临床结局变化相关。
