Haptoglobin (Hpt), primarily synthesized by hepatocytes, can be produced in central nervous system (CNS) under inflammatory conditions. In fact, increased Hpt was found in Cerebrospinal Fluids from patients with neurodegenerative diseases. We previously reported that Hpt binds Apolipoprotein E (ApoE), and influences ApoE key roles in cholesterol homeostasis. ApoE is the major constituent of lipoproteins into CNS, and modulates beta-Amyloid (A-beta) deposition and clearance. A-beta is known to trigger, in the brain, an inflammatory response, which is involved in the pathogenesis of Alzheimer's disease. Our aim was to verify whether Hpt affects the ApoE function in the regulation of A-beta accumulation in the brain. We report here that the abilities of Hpt and ApoE to bind A-beta are similar, and that Hpt enhances the binding of ApoE to A-beta, thus suggesting that the two proteins and A-beta might interact with each other to form a trimeric complex. Further, a SDS-stable complex between ApoE, Hpt, and A-beta is formed at 37°C, and A-beta aggregation is reduced when it is incubated in presence of Hpt and ApoE. Finally, we found that Hpt can bind astrocytes. In conclusion Hpt, as forming a trimeric complex with ApoE and A-beta, and binding astrocytes, might play a critical role, participating in the binding and clearance of A-beta, thus alleviating its toxicity and promoting its removal from the brain.

This work was funded by Compagnia di San Paolo "Neuroscience Programme"