Inflammation and alteration in lipid homeostasis are associated with the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD). Apolipoprotein E (ApoE), the main lipid carrier in brain, plays a key role in modulating lipid, beta amyloid (A-beta) and neuronal homeostasis. We previously showed that the acute-phase protein of inflammation Haptoglobin (Hpt) binds ApoE, and impairs its key function in cholesterol (chol) homeostasis in blood. Interestingly, increased level of Hpt was found in liquor from patients with AD and Parkinson's disease, and it was also found associated with A-beta plaques in AD. Hpt ability to inhibit A-beta fibril formation was reported. A main objective of our research was to study whether Hpt, because of its binding to ApoE, influences the ApoE function in A-beta and chol homeostasis. Also, the effect of aging on Hpt and ApoE expression in rat brains was investigated. Our results showed that Hpt influences A-beta clearance by astrocytes in culture. Also, Hpt affects the binding of ApoE to its neuronal and astrocytes receptors, which is essential for chol incorporation. A significant increase of Hpt level, associated with ApoE reduction was found in cortex and hippocampus of adults rats (24±2 weeks) compared to young rats (8±2 weeks). We suggest that the interaction between Hpt and ApoE might represent a mechanism by which inflammation affects AD pathogenesis.

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