The role of insulin resistance in the pathogenesis of Alzheimer's disease

Title

The role of insulin resistance in the pathogenesis of Alzheimer’s disease

Background

Many studies suggest that individuals with type 2 diabetes are at higher risk of developing Alzheimer´s disease (AD). It is therefore proposed that AD could be a brain-specific type of diabetes, type 3 diabetes. The hypothesis is that the brain is affected by high glucose levels and develop a resistance to insulin. Insulin resistance is usually associated with type 2 diabetes, however the dysfunction in regulating glucose metabolism also affects the neuronal circuits. This affects cognitive functions such as learning and memory abilities but can also cause a lot of stress and anxiety. AD is the most common form of dementia disorder and each year around 25,000 individuals in Sweden are diagnosed with AD. In type 2 diabetes, the peptide amylin aggregates and form amyloid containing plaques in the pancreas. Amylin is co-secreted with insulin to regulate blood glucose levels. Recent research has shown that patients with type 2 diabetes have similar accumulations of amyloid plaque in the pancreas that patients with AD have in their brain. Insulin degrading enzyme (IDE) is an enzyme responsible for both insulin and amyloid degradation. IDE regulates insulin levels in the blood. Thus, IDE could be a common factor. High levels of insulin may lead to decreased concentrations of IDE and this could indirectly contribute to amyloid accumulation in the brain. An early diagnosis of AD could mean better opportunities for preventative actions.

Purpose

The purpose of this project is aimed to better understand the relationship between insulin resistance and cognition to enable to identify individuals at risk for developing AD.

Method

This project includes establishing methods for identifying, measuring and validating IDE and other biological markers in patient samples related to both diabetes and dementia. Biological samples such as blood and saliva are collected from individuals and analyzes are mainly performed with ELISA (enzyme-linked immunosorbent assay) at Sophiahemmet research laboratory. Processing and comparisons of clinical data are done with statistical methods.

Importance

AD is preceded by a long (10–20 years) preclinical phase when changes occur gradually in the brain (including amyloid plaque accumulations). The disease process can last for many years before the first symptoms is apparent. Therefore, it may take some time before a lesser cognitive failure changes so much that the individual feels that everyday activities are affected. It is during this time frame when the changes in the brain are a fact before the cognitive failure becomes evident that there are likely opportunities to act before the onset of dementia symptoms. It is likely in this early phase of the disease that diagnostic biomarkers, which demonstrate the underlying disease process, would be most valuable.

Research Principal

Sophiahemmet University

Financier

Sophiahemmet Research Foundation

Contact

Project manager: Sciences Marie Svedberg, Associate Professor
Research group: Maria Kumlin, Professor of Medical, Helena Oreland, PhD student, all at Sophiahemmet University