Abstract
In this project, we are trying to review the articles that discuss the relationship between insulin signaling and Alzheimer's disease (AD). Another focus of this project is to find the best treatment regimen that can reduce the progression of AD in patients with impaired glucose metabolism. We used Pubmed database to collect our data and used the following keywords: Alzheimer’s disease, insulin signaling pathway, type 3 diabetes, type 2 diabetes, insulin, and insulin resistance in our revision; we included free articles that were published in the last 10 years and excluded articles that were written in any language other than English. We reviewed 68 articles. Forty-nine out of 68 articles were containing materials that are relevant for this project. We found that there is a relation between AD and the insulin signaling pathway. Insulin signaling pathway impairment leads to hyperphosphorylation of Tau protein, which plays a vital role in AD pathology. The effect of insulin on cognition is bidirectional; the intranasal route of insulin showed to have a promising effect on cognition improvement. Subcutaneous and intravenous insulin can increase the risk of dementia. Further studies are encouraged to use a specific anti-diabetic medication that can reduce the progression of AD.
Highlights
BackgroundAlzheimer's disease (AD) was first described in the second decade of the last century
We found that there is a relation between AD and the insulin signaling pathway
Insulin signaling pathway impairment leads to hyperphosphorylation of Tau protein, which plays a vital role in AD pathology
Summary
Alzheimer's disease (AD) was first described in the second decade of the last century. Studies showed that five to seven out of 10 dementia cases are due to AD This disease affects 44 million patients worldwide. Less than 10% of AD patients have a rapidly progressive disease course, which includes five to six points decline on Mini-Mental State Examination each year [21,22,23,24,25]. Binding of insulin to the IR activates tyrosine kinase enzyme in the beta-subunits and leads to phosphorylation of the tyrosine residues. A study from Sackler school of medicine showed that there is a relation between hemoglobin A1c levels and performance on cognitive tests as the following, A 1% higher hemoglobin A1C level was associated with a 1.75 point lower on digit symbol substitution test score, a 0.20 point lower on Mini-Mental Status Examination score, a 0.11 point lower memory score, and a worse score on the Stroop Test [33]. More studies are encouraged to determine the effect of sulfonylurea intake on cognition, as there are not enough studies available to determine the role of sulfonylurea [46]
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