Therapeutic Albumin Binding to Remove Amyloid-β

Clearance of plasma amyloid-beta (A beta) through plasma exchange and replacement with therapeutic albumin to facilitate net A beta efflux from the brain to plasma is a novel approach for the treatment of Alzheimer's disease. Therefore, thorough characterization of the capacity of therapeutic albumin to bind A beta is warranted. In this study, A beta(40) and A beta(42) were quantified by commercial ELISA or Araclon ABtest (R) in samples of Grifols' therapeutic albumin (Albutein (R)) 5%, 20%, and 25%. The capacity of Albutein (R) to bind A beta was assessed by: a) ELISA in serially diluted therapeutic albumin (0-45 mg/ml protein concentration) to which 80 pg/ml of synthetic A beta peptide (sA beta(40) or sA beta(42)) were added; b) ELISA in samples of the therapeutic albumin containing serially diluted sA beta(40) or sA beta(42) (60-400 pg/ml); and c) surface plasmon resonance (SPR) for sA beta(42) binding. The A beta content in Albutein (R) was below the quantification threshold of the ELISA tests (<25 to <62.5 pg/ml) and ABtest (R) (<3.125 pg/ml). Quantification of exogenously added sA beta(42) decreased in parallel with increasing protein concentration (59-78% at 45 mg/ml albumin). Recovery of sA beta serially diluted in Albutein (R) was similar to 60% for sA beta(40) and similar to 70% for sA beta(42), but was similar to 100% in control samples without albumin. The K-D by SPR analysis for sA beta(42) interaction with Albutein (R) was 1.72 +/- 0.24x10(-6) M. In conclusion, Grifols' therapeutic albumin has undetectable content of A beta(40) and A beta(42). Moreover, Grifols' therapeutic albumin consistently binds peptides containing the primary sequence of human A beta.