Jonathan Afiat and Leslie Kutner
PharmD Candidates University of Florida College of Pharmacy
The authors of Amylin Deposition in the Brain: A Second Amyloid in Alzheimer’s Disease? relate amylin accumulation to the development of AD. Research shows amylin and A-beta share a common mechanism of toxicity for their respected disease states via mitochondrial dysfunction. In this study, amylin oligomers and plaques were identified from diabetic patients but not controls; however the researchers noted that the participants were diabetics with AD, non-diabetics with AD and healthy controls.
From the article, it seems that the use of amylin would be deleterious for a patient with Alzheimer’s disease. In the study, endogenous human amylin accumulated within the brain, and the authors commented on how use of medications that increase the secretion of insulin/amylin could be harmful. All patients with AD, including type 2 diabetics and nondiabetics, had accumulation of amylin deposits and plaques within the brain; however, the plaques were larger and had a higher density in patients with type 2 diabetes. The mechanism behind this increase is thought to be hyperamylinemia and insulin resistance that requires increased insulin and amylin to be secreted into the circulatory system since hyperamylinemia is associated with increased plaque formation in the brain with subsequent brain cell damage, and synthetic amylin is absorbed systemically.
Endogenous amylin has the tendency to fold over on itself and oligemerize into amyloid which is insoluble. This will lead to plaque development and toxicity of beta cells. Symlin, a synthetic human amylin, has Proline substitutions to help prevent oligemerization and would likely not have a negative effect on a patient’s AD. Some discussions regarding Symlin and how it would affect endogenous amylin in type 2 diabetics theorized that the use of Symlin could cause negative feedback on the pancreas to slow/stop the release of endogenous amylin and subsequent plaque formation. However, there were no studies on Symlin and its effects on endogenous amylin or amyloid plaques.
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