A new study suggests insulin resistance in the brain can be an important factor for cognitive decline associated with Alzheimer’s.
Researchers from the Perelman School of Medicine at the University of Pennsylvania identified significant abnormalities in the activity of two major signaling pathways for insulin and insulin-like growth factor in non-diabetic people with Alzheimer’s disease.
Insulin is an important hormone in many bodily functions, including the health of brain cells. Researchers believe alterations in the insulin pathways could be targeted with new or existing medicines to potentially help resensitize the brain to insulin and possibly slow down or even reverse cognitive decline.
This is the first study to directly demonstrate that insulin resistance occurs in the brains of people with Alzheimer’s disease. The study is now online in the Journal of Clinical Investigation.
“Our research clearly shows that the brain’s ability to respond to insulin, which is important for normal brain function, is going offline at some point. Insulin in the brain not only modulates glucose uptake, but also promotes the health of brain cells — their growth, survival, remodeling, and normal functioning. We believe that brain insulin resistance may be an important contributor to the cognitive decline associated with Alzheimer’s disease,” said senior author Steven E. Arnold, M.D.
“If we can prevent brain insulin resistance from occurring, or resensitize brain cells to insulin with any of the currently available insulin-sensitizing diabetes medicines, we may be able to slow down, prevent, or perhaps even improve cognitive decline.”
Experts say the risk of developing Alzheimer’s disease increases by 50 percent in people with diabetes. Type 2 diabetes is due to insulin resistance and accounts for 90 percent of all diabetes.
Clinically, Type 2 diabetes (and Type 1 “juvenile” diabetes) is characterized by hyperglycemia — high levels of sugar in the blood — but there is no evidence that the brain in Alzheimer’s is hyperglycemic.
Investigators have determined that insulin acts differently in the brain than in the rest of the body. Researchers determined insulin resistance of the brain occurs in Alzheimer’s disease independent of whether someone has diabetes, by excluding people with a history of diabetes from this study.
To do this, investigators used samples of postmortem brain tissue from non-diabetics who had died with Alzheimer’s disease, stimulated the tissue with insulin, and measured how much the insulin activated various proteins in the insulin-signaling pathways.
There was less insulin activation in Alzheimer’s cases than in tissue from people who had died without brain disease. Other proteins linked to insulin action in the brain were abnormal in Alzheimer’s disease samples.
These abnormalities were highly correlated with episodic memory and other cognitive disabilities in the Alzheimer’s disease patients.
Researchers determined insulin resistance is another factor for cognitive decline different from the typical origin for Alzheimer’s disease.
However, three insulin-sensitizing medicines are already approved by the FDA for treatment of diabetes. These drugs readily cross the blood-brain barrier and may have therapeutic potential to correct insulin resistance in Alzheimer’s disease and mild cognitive impairment (MCI).
“Clinical trials would need to be conducted to determine the impact the drugs have on Alzheimer’s disease and MCI in non-diabetic patients,” said Arnold.
Source: University of Pennsylvania