Covalent immobilization of human serum albumin on cellulose acetate membrane for scavenging amyloid beta - A stepping extracorporeal strategy for ameliorating Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by interrupted neurocognitive functions and impaired mental development presumably caused by the accumulation of amyloid beta (A beta) in the form of plaques. Targeting A beta has been considered a promising approach for treating AD. In the current study, human serum albumin (HSA), a natural A beta binder, is covalently immobilized onto the surface of a cellulose acetate (CA) membrane to devise an extracorporeal A beta sequester. The immobilization of HSA at 3.06 +/- 0.22 mu g/mm(2 )of the CA membrane was found to be active functionally, as evidenced by the esterase-like activity converting pnitrophenyl acetate into p-nitrophenol. The green fluorescent protein-A beta (GFP-A beta) fusion protein, recombinantly produced as a model ligand, exhibited characteristics of native A beta. These features include the propensity to form aggregates or fibrils and an affinity for HSA with a dissociation constant (K-D) of 0.91 mu M. The HSA on the CA membrane showed concentration-dependent sequestration of GFP-A beta in the 1-10-mu M range. Moreover, it had a greater binding capacity than HSA immobilized on a commercial amine-binding plate. Results suggest that the covalent immobilization of HSA on the CA surface can be used as a potential platform for sequestering A beta to alleviate AD.