Is There Inflammatory Synergy in Type II Diabetes Mellitus and Alzheimer’s Disease?

Figure 2

RAGE-driven inflammatory synergy in Alzheimer’s disease with type 2 diabetes mellitus. Receptor for advanced glycation endproducts- (RAGEs) mediated inflammatory responses play an important roles in pathogenesis of Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM). In AD, A𝛽 is the most prominent ligand that interacts with RAGE leading to inflammatory signaling. The interaction also leads to microglia secretion of M-CSF which can further upregulate the expression of RAGE in microglia. Other inflammatory cytokines and chemokines are also produced upon the activation of RAGE, including IL-1𝛽, IL-6, TNF-𝛼, and MCP-1. Several of these inflammatory mediators also can modulate the expression of RAGE and its ligands. A number of other ligands are also expressed at elevated levels in the AD brain including AGE, S100A8, S100A9, S100A12, S100B, and HMG1. In T2DM, advanced glycation endproducts (AGEs) are the major ligand. Interaction with RAGE, AGE induces production of other RAGE ligands and inflammatory cytokines and chemokines, which is the major mechanism for propagation of vascular inflammatory injury in T2DM-associated vascular diseases. Thus, RAGE-mediated inflammatory responses might be accentuated when these two diseases coexist in the same patient.