Amyloid-targeted therapeutics in Alzheimer's disease: Use of human albumin in plasma exchange as a novel approach for abeta mobilization

Abstract

A clinical investigation program was carried out to replace endogenous albumin of patients with mild to moderate Alzheimer's disease (AD) with 5% Human Albumin Grifols(R) through a plasma exchange (PE) schedule, in order to alter the dynamic equilibrium between albumin-bound Abeta in plasma and Abeta in cerebrospinal fluid. In a pilot proof-of-concept study, 7 patients underwent 6 PE in 3 weeks and 1 year of follow-up. Plasma Abeta determinations demonstrated a variation pattern in levels in relation with the PEs. Cognitive status scores (MMSE and ADAS-Cog) were more stable than expected. In a phase II clinical trial, 29 patients were randomized into PEtreated and control groups with 1 year follow-up. Interim results point toward the occurrence of Abeta40 mobilization in the PE-treated patients, who scored better in cognitive tests (differences at 9 months: 2.5 in MMSE and 5.5 in ADAS-cog). These results suggest that a PE program with 5% Human Albumin Grifols may have a promising role in the treatment of mild to moderate AD.