Human serum albumin (HSA) is the major carrier of A beta peptides in blood plasma. 1:1 interaction stoichiometries were established in previous indirect antibody-based studies for both A beta 40 and A 42, but corresponding binding constants were not provided. In this study we applied direct titrations of HSA with A beta 40 monitored using circular dichroism spectroscopy and obtained a dissociation constant (K-d) of 5 +/- 1 mu M for a HSA complex with A beta 40. The interaction resulted in an increase of the a-helical contents in the complex, compared to its components, which is quantitatively consistent with the known ability of A beta 40 to adopt a partially a-helical conformation in a hydrophobic environment. The relevance of these findings for the role of HSA in A beta physiology is discussed. (C) 2007 Elsevier Inc. All rights reserved.