AMBAR Therapeutic plasma exchange

AMBAR is an innovative clinical trial aimed at slowing down the progression of Alzheimer’s disease through periodic therapeutic plasma exchange.

AMBAR targets a multimodal approach to the management of the disease based on the hypothesis that most of the amyloid-beta protein is bound to albumin and circulates in plasma. Extracting this plasma may flush amyloid-beta peptide from the brain into the plasma, thus potentially limiting the disease’s impact on the patient’s cognitive functions. Additionally, albumin has binding capacity and antioxidant properties, and both albumin and immunoglobulin display immunomodulatory and anti-inflammatory properties.

Based on this hypothesis, the build-up of beta-amyloid could be reduced before it can cause neuronal damage, thus potentially limiting the impact of Alzheimer’s disease on cognition.


Results of the AMBAR trial

transfusion bag set-up


This phase 2b/3 trial examined the effects of plasma exchange (PE) in patients with mild‐to‐moderate Alzheimer’s disease (AD).


Three hundred forty‐seven patients (496 screened) were randomized (1:1:1:1) into three PE treatment arms with different doses of albumin and intravenous immunoglobulin replacement (6‐week period of weekly conventional PE followed by a 12‐month period of monthly low‐volume PE), and placebo (sham).


PE‐treated patients performed significantly better than placebo for the co‐primary endpoints: change from baseline of Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS‐ADL; P = .03; 52% less decline) with a trend for Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS‐Cog; P = .06; 66% less decline) scores at month 14. Moderate‐AD patients (baseline Mini‐Mental State Examination [MMSE] 18‐21) scored better on ADCS‐ADL (P = .002) and ADAS‐Cog (P = .05), 61% less decline both. There were no changes in mild‐AD patients (MMSE 22‐26). PE‐treated patients scored better on the Clinical Dementia Rating Sum of Boxes (CDR‐sb) (P = .002; 71% less decline) and Alzheimer’s Disease Cooperative Study‐Clinical Global Impression of Change (ADCS‐CGIC) (P < .0001; 100% less decline) scales.


This trial suggests that PE with albumin replacement could slow cognitive and functional decline in AD, although further studies are warranted.