New research has shown that impaired insulin signaling in the brain, often a feature of diabetes, may negatively impact cognition, mood, and metabolism — all of which are common aspects of Alzheimer’s disease.
However, the mechanisms behind this relationship have remained hidden.
A recent study investigated the impact of blocking insulin receptors and insulin-like growth factor (IGF1) receptors in mouse models.
The work was carried out at the Joslin Diabetes Center, affiliated with Harvard Medical School in Boston, MA. The results reveal that interrupting these similar pathways impaired both learning and memory.
The researchers published their findings in the Proceedings of the National Academy of Sciences.
The researchers worked with both the hippocampus and the central amygdala, areas of the brain that help with cognition function, as well as metabolic control.
They looked into how mice with disabled insulin and IGF1 receptors tackled mazes, and the results were revealing.
First, the researchers allowed the mice to explore the maze to familiarize themselves with its layout, and then they blocked a pathway before reintroducing the mice to the labyrinth.
These particular mice failed to analyze the new barricade and instead tried to go through the maze as if it was the way it had always been.
Senior author C. Ronald Kahn, chief academic officer at Joslin and the Mary K. Iacocca Professor of Medicine at Harvard Medical School, notes that this is the first study that shows a relationship between these disrupted pathways and cognition problems.
He says, “Since these two receptors can partially compensate for one another, what we did that was critical was this combined insulin and IGF receptor knockout.”
Prof. Kahn goes on to explain, “However, it was also important to do it in specific regions, since if it was everywhere it might have impaired brain development. By knocking out both [receptors], we removed not only the primary way they work but the backup system that’s already built in.”
Alzheimer’s disease is the most common cause of dementia, which is when a person is experiencing memory loss and other cognition issues that are severe enough to interfere with daily life.
Alzheimer’s, though, is not a normal part of aging, and while most of those who have it are 65 years of age and older, it can affect people who are younger.
Alzheimer’s does not get better over time, and, in most cases, it tends to worsen until the person loses the ability to carry on a conversation or respond to what is happening around them.
There is no cure for the condition, but there are treatments available that can slow down progression and may improve the individual’s overall quality of life.
There are risk factors that scientists have associated with developing Alzheimer’s disease. There are some factors that people cannot control, for example, age, family history, and genetics. People might be able to influence other potential causes, however, including head injuries and heart disease.
Additionally, diabetes is a known risk factor for Alzheimer’s disease. Other studies have shown a connection between insulin pathways and premature cognitive decline, dementia, depression, and anxiety.
Also, studies have helped demonstrate that abnormal receptors are present more often in those who have both Alzheimer’s and type 2 diabetes.
The current study is the first to target specific regions to help determine cause and effect.
Next, the researchers want to look at what happens when they cross the mice they used in this study with mice that are genetically prone to developing Alzheimer’s.
Investigating these connections, they say, may lead to recommendations of lifestyle changes well before a disease process even begins.
“With diabetes and obesity, there is resistance in these pathways and, therefore, we think that this could be an important factor as to why people with Alzheimer’s disease and diabetes have a faster-accelerated course or have more Alzheimer’s disease.”
Senior author C. Ronald Kahn