Copper Mediated Affinity of Amyloid β to Chondroitin Sulfates

Abstract

Aβ is a major component of the senile plaques characteristic of Alzheimer disease (AD) and sulfated GAGs such as chondroitin sulfates (CS) have been found in all types of amyloidosis. In this paper, a biochromatographic approach was developed to measure for the first time changes in enthalpy, heat capacity change and copper effect for the binding of Aβ to CS in a wide temperature range. For this, CS was immobilized on a chromatographic support. It was established that this novel CS column was stable during an extended period of time. The thermodynamic data showed that Aβ–CS binding, for low temperature (<10 °C), is enthalpically unfavourable and being dominated by a positive entropy change. This result suggested that dehydration at the binding interface and charge–charge interactions contribute to the Aβ–CS complex formation and a large heat capacity change, ΔC p = −2.32 kJ mol−1 K−1, was determined. Above 10 °C, the thermodynamic data ΔH and ΔS became negative due to van der Waals interactions and hydrogen bonding which are engaged at the complex interface confirming strong Aβ–CS hydrogen bond networks. Also, for a copper concentration in the range 20–160 μM, it was shown that an increase of the Cu2+ concentration in the medium led an increase of this association classically attributed to salt effect (i.e. hydrophobic bonds) and to ion pair formations between the Cu2+ cation and Aβ to bind to chondroitin sulfate and could thus improve the Aβ aggregation by copper.