Bridging Pancreatic Amyloidosis and Neurodegeneration: The Emerging Role of Amylin in Diabetic Dementia

A hallmark of type 2 diabetes mellitus is the presence of abundant amyloid deposits composed of islet amyloid polypeptide (also known as amylin) in the pancreatic islets of Langerhans. Given the conspicuous prevalence of these deposits in diabetic patients, it was long assumed that human islet amyloid polypeptide fibrillization plays a crucial pathogenic role in type 2 diabetes mellitus. Amylin, which is co-secreted with insulin, can accumulate and induce β-cell toxicity, thereby reducing insulin secretion and precipitating overt (insulin-dependent) diabetes. Growing evidence suggests that amylin also accumulates in the brains of Alzheimer’s disease patients and may interact with amyloid-β to exacerbate neurodegeneration. Although the precise mechanisms are unclear, type 2 diabetes mellitus can alter cerebrovascular hemodynamics, potentially triggering early dementia symptoms and accelerating neurodegeneration. In this review, we highlight recent evidence suggesting that pancreatic β-cell amylin aggregation might be an early indicator of dementia in type 2 diabetes mellitus patients. We also evaluate the relationships between amylin aggregation and various proteostasis-associated proteins in β-cells, which may inform prospective diagnostic and therapeutic strategies for “diabetic dementia” from an amylin-centric perspective.