LAUSR

Type II Diabetes (T2D) is a major risk factor for Alzheimer's Disease (AD). These two diseases share several pathological features including amyloid accumulation, inflammation, oxidative stress, cell death and cognitive decline. The metabolic hormone amylin and amyloid beta are both amyloids known to self-aggregate in T2D and AD, respectively, and are thought to be the main pathogenic entities in their respective diseases. Furthermore, studies suggest amylin's ability to seed amyloid beta aggregation, the activation of common signaling cascades in the pancreas and the brain, and the ability of amyloid beta to signal through amylin receptors (AMYR), at least in vitro. However, paradoxically, non-aggregating forms of amylin such as pramlintide are given to treat T2D and functional and neuroprotective benefits of amylin and pramlintide administration have been reported in AD transgenic mice. These paradoxical results beget a deeper study of AMYR changes and signaling in T2D to be able to fully understand its potential role in mediating AD development or prevention. The AMYR is composed of the Calcitonin Receptor complexed to a Receptor Activity Modifying Protein (RAMP). Studies have shown that RAMPs 1 & 3 are the two isoforms most responsible for signaling in the brain. However, how, specifically, amylin signals through these two isoforms to potentially drive toxicity or neuroprotection remains unknown. The goal of this review is to summarize the known functions of amylin through different biological systems and to begin to elucidate the relationship between T2D, AMYR signaling, and how these factors may influence mechanisms of AD pathogenesis.