Amyloid-β Activates Microglia and Regulates Protein Expression in a Manner Similar to Prions

Prions are the only convincingly demonstrated proteinaceous infectious particle, yet recent studies find that amyloid-beta peptide (A beta) aggregates are capable of self-propagation, which induces amyloidosis pathology in Alzheimer's disease (AD) model mice that is similar to the self-propagation phenomenon of prions in neurons. Gliosis is a common hallmark of AD and prion diseases, in which activated microglia accumulate around abnormal protein deposits. Analyses of the characteristics of activated microglia induced by A beta in comparison with those induced by prions will provide new insight into the pathogenesis of AD. Therefore, we compared the characteristics of BV-2 cells (model microglia) activated by A beta fibrillar peptides (A beta 1-42) and prions (PrP106-126). A beta 1-42 and PrP106-126, as well as the supernatants of the media collected from BV-2 cells cocultured with A beta 1-42 and PrP106-126, were potent activators of BV-2 microglial activity, but the chemotaxis index (CI) induced by A beta 1-42 was significantly higher than that induced by PrP106-126 at each concentration. A beta 1-42 and PrP106-126 increased the proliferation index (PI) and upregulated monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor beta 1 (TGF-beta 1) expression after 12 h of exposure. Our results show that A beta activates microglia and regulates microglial protein expression in a manner similar to prions and, thus, provide new insight into the pathogenesis of AD.