Targeting Insulin- and Calcium-related Pathways for Potential Treatments for Alzheimer's Disease and Diabetes

Alzheimer's disease and diabetes are common disorders among the elderly population and have emerged as a major health concern. Both diseases pose considerable risks to one another. Diabetics have a significantly increased probability of getting Alzheimer's disease throughout their lifetime. These diseases are linked because, both share common risk factors such as impaired carbohydrate metabolism, insulin resistance, oxidative stress, inflammatory response, mitochondrial dysfunction, and amyloidosis. Insulin is a vital hormone responsible for bringing extremely high glucose levels back to normal and its receptors available in the hippocampus help in enhancing cognitive function. Insulin resistance consequently serves as a link between both diabetes and AD. Similarly, amylin is another hormone secreted by the pancreas along with insulin. During diabetes, amylin gets oligomerized and forms a neurotoxic complex with Aβ inside the brain, which causes AD to develop. Along with these, another main mechanism influencing AD development is Ca²⁺ dyshomeostasis. Insulin production from the pancreas is generally aided by Ca²⁺, but in excess, it can cause dysregulation of many signaling pathways such as CaMKK2, CAMP, CREB, MAPK, STIM\Orai, etc. which can ultimately result in the pathogenesis of AD in diabetic people. In this review, we discussed in detail the pathogenesis of AD associated with diabetes and the mechanisms initiating their progression.