Grifols' recent Alzheimer Management by Albumin Replacement ("AMBAR") study investigated the effects of plasmapheresis with albumin replacement, plus intravenous immunoglobulin (IVIG) in some subjects, in patients with mild-to-moderate Alzheimer's disease (AD). AMBAR was a phase IIb trial in the United States and a phase III trial in Europe. There were three treatment groups (plasmapheresis with albumin replacement; plasmapheresis with low dose albumin and IVIG; plasmapheresis with high dose albumin and IVIG) and sham-treated controls. Disease progression in pooled treated patients was 66% less than control subjects based on ADAS-Cog scores (p = 0.06) and 52% less based on ADCS-ADL scores (p = 0.03). Moderate AD patients had 61% less progression, based on both ADAS-Cog and ADCS-ADL scores, than their sham-treated counterparts (p-values 0.05 and 0.002), and their CDR-Sb scores declined 53% less than their sham-treated counterparts. However, ADAS-Cog and ADCS-ADL scores were not significantly different between actively-treated and sham-treated mild AD patients, although CDR-Sb scores improved vs. baseline for treated mild AD patients. Patients administered both IVIG and albumin had less reduction in brain glucose metabolism than sham-treated patients. Questions raised by these findings include: what mechanism(s) contributed to slowing of disease progression? Is this approach as effective in mild AD as in moderate AD? Must IVIG be included in the protocol? Does age, sex, or ApoE genotype influence treatment response? Does the protocol increase the risk for amyloid-related imaging abnormalities? How long does disease progression remain slowed post-treatment? A further study should allow this approach to be optimized.

中文翻译：

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AMBAR，一个引起问题的令人鼓舞的阿尔茨海默氏症试验。

Grifols最近通过白蛋白替代治疗阿尔茨海默氏病（“ AMBAR”）研究调查了血浆置换与白蛋白替代以及静脉注射免疫球蛋白（IVIG）在轻度至中度阿尔茨海默氏病（AD）患者中的作用。AMBAR在美国是IIb期试验，在欧洲是III期试验。有三个治疗组（用白蛋白置换的血浆置换；用低剂量白蛋白和IVIG进行血浆置换；用高剂量白蛋白和IVIG进行血浆置换）和假治疗的对照组。基于ADAS-Cog评分，合并治疗患者的疾病进展比对照组低66％（p = 0.06），基于ADCS-ADL评分，疾病进展比对照组低52％（p = 0.03）。根据ADAS-Cog和ADCS-ADL评分，中度AD患者的进展减少了61％，较假手术的同龄人（p值0.05和0.002），其CDR-Sb得分下降了53％。然而，积极治疗和假治疗轻度AD患者之间的ADAS-Cog和ADCS-ADL评分无显着差异，尽管相对于基线，轻度AD患者的CDR-Sb评分有所改善。与假治疗的患者相比，同时使用IVIG和白蛋白的患者的脑部葡萄糖代谢降低的幅度较小。这些发现提出的问题包括：导致疾病进展减慢的机制是什么？这种方法在轻度AD和中度AD一样有效吗？协议中必须包含IVIG吗？年龄，性别，或ApoE基因型影响治疗反应？该协议是否增加了淀粉样蛋白相关成像异常的风险？治疗后疾病进展会持续多长时间？进一步的研究应允许优化此方法。