Biomarkers of neuroinflammation: Focus on monocyte chemotaxis

Abstract

According to the amyloid cascade hypothesis, beta-amyloid (Abeta) aggregation represents the core pathogenic mechanism in Alzheimer's disease (AD). Neuroinflammation, as an inflammatory process confined to the CNS, plays a key role as well, fueling a response against Abeta, and eventually further damaging the surrounding neurons. Research currently points out at microglia cells as the central players of this game. However, an important role for periphery should be advocated, since peripheral blood monocytes cross the blood-brain barrier (BBB) attracted by Abeta and chemokines, and contribute to neuroinflammation by transforming into blood-born macrophages. Interestingly, this process of “neuroinvasion” from periphery represents the afferent arc of the inflammatory reflex, regulating a response against protein aggregates. The efferent arc is represented by a vagal cholinergic pathway projecting onto alpha7nAChR expressed by spleen mononuclear cells for shutting off the inflammasome and so modulating the process. In this talk we will focus on the role of peripheral monocytes, and in particular on the process of chemotaxis and neuroinvasion. Attention will be also given to the expression of the monocyte chemotactic systems, and among them, in particular, to the TSPO receptor (marker of activated microglia) and of the cognate biological ligand, the Diazepam Binding Inhibitor (DBI).