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

A key event of Alzheimer's disease (AD) pathogenesis is the production of amyloid beta peptides (A beta), 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 A beta on human DC functions. Myeloid DCs differentiated in the presence of A beta 42 showed an increase in survival and soluble antigen uptake, a reduction in HLA molecule expression and in IL-10 and IL-12 production. Accordingly, A beta 42-treated DCs were impaired in inducing T cell proliferation and IL-2 production. On the other hand, A beta 42 treatment provided DCs with the ability to release higher levels of IL-1 beta, IL-6 and IL-18, than control DCs. These results demonstrate that A beta 42 can modulate the immune system by inducing pro-inflammatory DC differentiation, thus gaining new insights into AD pathogenesis and immune-based therapeutic intervention.