Treatment of Alzheimer disease using combination therapy with plasma exchange and haemapheresis with albumin and intravenous immunoglobulin: Rationale and treatment approach of the AMBAR (Alzheimer Management By Albumin Replacement) study

Introduction: There is a growing interest in new therapeutic strategies for the treatment of Alzheimer disease (AD) which focus on reducing the beta-amyloid peptide (4) burden in the brain by sequestering plasma A beta, a large proportion of which is bound to albumin and other proteins. This review discusses the concepts of interaction between A beta and albumin that have given rise to AMBAR (Alzheimer's Disease Management by Albumin Replacement) project, a new multicentre, randomised, controlled clinical trial for the treatment of AD. Development: Results from preliminary research suggest that Albutein (R) (therapeutic albumin, Grifols) contains no quantifiable levels of A beta. Studies also show that Albutein (R) has A beta binding capacity. On the other hand, AD entails a high level of nitro-oxidative stress associated with fibrillar aggregates of A beta that can induce albumin modification, thus affecting its biological functions. Results from the phase a study confirm that using therapeutic apheresis to replace endogenous albumin with Albutein (R) 5% is feasible and safe in patients with AD. This process resulted in mobilisation of AB and cognitive improvement in treated patients. The AMBAR study will test combination therapy with therapeutic apheresis and haemopheresis with the possible leverage effect of Albutein (R) with intravenous immunoglobulin replacement (Flebogamma DIF). Cognitive, functional, and behavioural changes in patients with mild to moderate AD will be assessed. Conclusions: the AMBAR study represents a new therapeutic perspective for AD. (C) 2014 Sociedad Espanola de Neurologia. Published by Elsevier Espana, S.L.U. All rights reserved.