Amyloid β peptide promotes differentiation of pro-inflammatory human myeloid dendritic cells

A key event of Alzheimer's disease (AD) pathogenesis is the production of amyloid β peptides (Aβ), which are hypothesized to lead to neurodegeneration by still unclear mechanisms, including a chronic inflammatory response characterized by innate immune cell activation and pro-inflammatory molecule release. Since dendritic cells (DCs) are central players of innate immune response and brain dendritic-like cells may have a crucial role in AD pathogenesis, this study investigates the effects of Aβ on human DC functions. Myeloid DCs differentiated in the presence of Aβ42 showed an increase in survival and soluble antigen uptake, a reduction in HLA molecule expression and in IL-10 and IL-12 production. Accordingly, Aβ42-treated DCs were impaired in inducing T cell proliferation and IL-2 production. On the other hand, Aβ42 treatment provided DCs with the ability to release higher levels of IL-1β, IL-6 and IL-18, than control DCs. These results demonstrate that Aβ42 can modulate the immune system by inducing pro-inflammatory DC differentiation, thus gaining new insights into AD pathogenesis and immune-based therapeutic intervention.