Isothermal titration calorimetry (ITC) is one of the most powerful means for direct determination of thermodynamic information associated with most physiochemical and biological processes. The deposition and aggregation of beta-amyloid (A beta) on cell membranes was considered as one of the primary factors in having Alzheimer's disease (AD). Recently, a growing body of evidence has suggested that plasma membrane could accelerate the accumulation of A beta on the plasma membranes. However, the mechanism of AD is still a controversial issue. This study provided a biothermodynamic approach to real-time monitor the heat of metabolism involved in the co-incubation of PC12 cells and A beta(1-40) by ITC. The effects of A beta conformation and concentration of oligomeric A beta on cytotoxicity were successfully distinguished by ITC. This approach with rapid and direct measurement may provide not only real-time information for the effects of A beta species on living cells but also a platform for the screening of drug candidates for AD. (C) 2010 Elsevier B.V. All rights reserved.