IS INSULIN A KEY TO ALZHEIMER’S DISEASE?

Doctors have known for some time that the production of too little insulin by the pancreas and the inability of the cells throughout the body to respond to insulin (insulin resistance) are the hallmarks of type 1 and type 2 diabetes, respectively.

While the relationship between insulin and diabetes is well known, a more recent discovery is the role it plays in regulating brain functions such as the ability to learn and make new memories and to store and recall events. Scientists have also discovered that people with Alzheimer's disease have fewer insulin receptors than healthy patients.

Another intriguing finding: Insulin affects the brain's ability to clear away beta-amyloid-42 (Aß42), the toxic protein that builds up into plaques in the brain. These plaques, along with tangles of another protein called tau, located within cells, are telltale signs of Alzheimer's disease.

The suggestive evidence linking insulin to Alzheimer's disease may help explain why people with diabetes have a greater risk of experiencing cognitive decline and future dementia than individuals who don't have diabetes.

A gateway to the brain. Some researchers now believe that just as insulin is an effective treatment for diabetes, it might also be a useful therapy for Alzheimer's disease. The challenge: getting it to the brain without affecting blood glucose levels, as insulin injections would do. One potential answer: a nasal spray that is inhaled, allowing it to reach the brain within a few minutes, with minimal absorption into the bloodstream.

While recent studies suggest that intranasal insulin therapy may be safe and effective, there are important considerations to keep in mind. First, most studies have been small and have focused on short-term use. Consequently, the safety and effectiveness of intranasal insulin use over an extended period are unknown.

Second, intranasal insulin doesn't work for everyone, but it's not clear why. Some evidence suggests that genetics may play a role. For example, a small 2008 study in the Journal of Alzheimer's Disease found that memory improved after insulin treatment in study participants who did not carry the APOE-ε4 gene -- a known risk factor for late-onset Alzheimer's disease. In those with the APOE-ε4 gene, however, memory deteriorated. Findings from this study raise another potentially troubling concern. Intranasal insulin increased blood levels of Aß42 -- the toxin implicated in the development of late-onset Alzheimer's disease. This may indicate that the insulin was working by removing the protein from the brain and having it removed by the bloodstream, but other reasons are possible.

(Source:  John Hopkins Health Alert, posted in Diabetes on 13 March 2013)