Grant: Project Grant

A healthy brain requires a healthy body. It is increasingly recognized that by improving the body's general metabolism, one can also improve brain function. This may be particularly true for Alzheimer's disease (AD). Over the last 20 years, we have learned that metabolic diseases such as diabetes, along with poor lifestyle habits, increase the risk of developing AD. Insulin-like growth factor-binding protein 2 (IGFBP2) is a metabolic hormone associated with diabetes, which can affect both the body and the brain. Blood levels of IGFBP2 show complex patterns: while they decrease in diabetes and obesity, they tend to increase with age and in patients with AD. In recent years, our group has investigated IGFBP2 levels in the blood of people before they show signs of AD. We have found that IGFBP2 not only increases as AD develops but is also closely linked to memory and thinking abilities, as well as other markers of the disease. Additionally, we have discovered that IGFBP2 in the blood can reach the brain and influence its function. In this proposal, we plan a thorough series of experiments to determine the true potential of IGFBP2-whether it could serve as a treatment for AD or if it might have harmful effects. First, we will investigate whether IGFBP2 can serve as an early indicator of AD or help identify people who might benefit from antidiabetic treatments to prevent AD. Second, to explore the underlying mechanisms, we will conduct studies in animals treated with IGFBP2 to assess its effects on brain pathology and cognition. In summary, the results of this project will reveal whether this key hormone, IGFBP2, can be leveraged to prevent or slow the progression of AD.