Insulin resistance in the brain is the largest contributing factor to cognitive decline in people with Alzheimer’s disease, according to researchers at the Perelman School of Medicine. Insulin is a well known, important hormone in the body involved in protein synthesis and blood sugar regulation. Without it people can develop a multitude of issues – this is known as Diabetes Type 1.
The researchers discovered abnormalities in the signalling for insulin and insulin like growth factor (IGF) in non-diabetic Alzheimer’s patients.
“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” Steven E Arnold, MD, Professor of Psychiatry and Neurology
People with diabetes are 50% more likely to develop Alzheimer’s in old age. This is generally to do with Diabetes Type 2, which is caused by insulin resistance to excessive insulin release. Insulin’s function in the brain is different to that of other cells (muscle and adipose tissue) meaning that there is more at stake than simply activating glucose transporters or upregulating protein synthesis.
The research involved using post-mortem brain samples of non-diabetic patients, then stimulating those samples with insulin and measuring the activity of various proteins. In patients with Alzheimer’s there was far less protein activity and other proteins linked to physiological insulin activity were also decreased in Alzhimer’s samples.
The researchers were able to determine that there were significant changes to the protein – insulin receptor substrate-1 (IRS-1) in brain cells regardless of sex, age, diabetes or apolipoprotein E gene status. IRS-1 undergoes serine phosphorylation to become IRS-1pSer, which is common in people with diabetes and Alzheimer’s.
The level of IRS-1 was also associated with the presence of amyloid-β plaques – a common sign of Alzheimer’s disease. More information can be found here: New Alzheimer’s Marker Can Predict Mental Decline.
The researchers believe that insulin sensitizing drugs, currently approved by the FDA, will be of some benefit and will aid in slowing down the rate of cognitive decline in people already suffering from Alzheimer’s. More research will need to be done to prove that claim, however, it is an exciting leap forward in the palliative treatment of Alzheimer’s.