Human serum albumin (HSA) serves as a natural depot of amyloid beta peptide (A beta). Improvement of A beta binding to HSA should impede Alzheimer's disease (AD). We developed a method for quantitation of the interaction between monomeric A beta 40/42 and HSA using surface plasmon resonance spectroscopy. The dissociation constant of HSA complex with recombinant A beta 40/42 is 0.2-0.3 mu M. Flemish variant of A beta 40 has 2.5-10-fold higher affinity to HSA. The parameters of the HSA-A beta interaction are selectively sensitive to HSA binding of major plasma unsaturated fatty acids and Cu2+. Linoleic and arachidonic acids promote the HSA-A beta 42 interaction. The developed methodology for quantitation of HSA-A beta interaction may serve as a tool for search of compounds favoring HSA-A beta interaction, thereby preventing AD progression. (C) 2019 Elsevier Inc. All rights reserved.