title: 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.
abstract: BACKGROUND
  There is a growing interest in new therapeutic strategies for the treatment of Alzheimer disease (AD) which focus on reducing the beta-amyloid peptide (Aβ) burden in the brain by sequestering plasma Aβ, a large proportion of which is bound to albumin and other proteins. This review discusses the concepts of interaction between Aβ 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.
  
  
  METHODS
  Results from preliminary research suggest that Albutein(®) (therapeutic albumin, Grifols) contains no quantifiable levels of Aβ. Studies also show that Albutein(®) has Aβ binding capacity. On the other hand, AD entails a high level of nitro-oxidative stress associated with fibrillar aggregates of Aβ that can induce albumin modification, thus affecting its biological functions. Results from the phase ii study confirm that using therapeutic apheresis to replace endogenous albumin with Albutein(®) 5% is feasible and safe in patients with AD. This process resulted in mobilisation of Aβ 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(®) 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.
authors.affiliation: Fundació ACE, Institut Català de Neurociències Aplicades, Barcelona, España; Hospital Universitari Vall d'Hebron-Institut de Recerca, Universitat Autònoma de Barcelona (VHIR-UAB), Barcelona, España. Electronic address: mboada@fundacioace.com.
authors.forename: M
authors.initials: M
authors.lastname: Boada
authors.affiliation: Laboratorio de Fisiología Molecular y Canalopatías, Departamento de Ciencias Experimentales y de la Salud, Universitat Pompeu Fabra, Barcelona, España.
authors.forename: E
authors.initials: E
authors.lastname: Ramos-Fernández
authors.affiliation: Laboratorio de Fisiología Molecular y Canalopatías, Departamento de Ciencias Experimentales y de la Salud, Universitat Pompeu Fabra, Barcelona, España.
authors.forename: B
authors.initials: B
authors.lastname: Guivernau
authors.affiliation: Laboratorio de Fisiología Molecular y Canalopatías, Departamento de Ciencias Experimentales y de la Salud, Universitat Pompeu Fabra, Barcelona, España.
authors.forename: F J
authors.initials: FJ
authors.lastname: Muñoz
authors.affiliation: Área de Investigación y Desarrollo, Grifols, Barcelona, España.
authors.forename: M
authors.initials: M
authors.lastname: Costa
authors.affiliation: Área de Investigación y Desarrollo, Grifols, Barcelona, España.
authors.forename: A M
authors.initials: AM
authors.lastname: Ortiz
authors.affiliation: Área de Investigación y Desarrollo, Grifols, Barcelona, España.
authors.forename: J I
authors.initials: JI
authors.lastname: Jorquera
authors.affiliation: Departamento de Ensayos Clínicos y Farmacovigilancia, Grifols, Barcelona, España.
authors.forename: L
authors.initials: L
authors.lastname: Núñez
authors.affiliation: Departamento de Ensayos Clínicos y Farmacovigilancia, Grifols, Barcelona, España.
authors.forename: M
authors.initials: M
authors.lastname: Torres
authors.affiliation: Departamento de Ensayos Clínicos y Farmacovigilancia, Grifols, Barcelona, España.
authors.forename: A
authors.initials: A
authors.lastname: Páez
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000737:chemistry / Q000302:isolation & purification* / Q000627:therapeutic use*; D000544:Alzheimer Disease / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D010951:Plasma Exchange / Q000379:methods*; D010956:Plasmapheresis / Q000379:methods*; D011485:Protein Binding
chemical_list: D000418:Albumins; D016229:Amyloid beta-Peptides; D016756:Immunoglobulins, Intravenous
keywords: Albumin; Albúmina; Alzheimer disease; Beta amyloid peptide; Enfermedad de Alzheimer; Haemapheresis; Hemoféresis; Inmunoglobulina intravenosa; Intravenous immunoglobulin; Plasmaféresis; Plasmapheresis; Péptido betaamiloide