A Northwestern University-led research team reported that insulin may slow or prevent the damage and memory loss in Alzheimer’s disease by shielding memory-forming synapses from harm. Their findings, published in the Proceedings of the National Academy of Sciences, found that insulin blocked damage to memory-forming synapses from toxic proteins that attack them.

 

Scientists treated neurons taken from the hippocampus with insulin and the insulin-sensitizing drug rosiglatizone (Avandia), which has been used to treat type 2 diabetes. These cells are susceptible to damage caused by amyloid beta-derived diffusible ligands of ADDLs, toxic proteins that build up in Alzheimer’s patients. After ADDL binding, synapses lose their capacity to respond to incoming information, resulting in memory loss. The researchers discovered that damage to neurons exposed to ADDLs was blocked by insulin, which kept the protein from attaching to the cells by removing ADDL receptors. They also found that protection by low levels of insulin was enhanced by rosiglitazone.

 

“Recognizing that Alzheimer’s disease is a type of brain diabetes points the way to novel discoveries that may finally result in disease-modifying treatments for this devastating disease,” says Sergio Ferreira, a professor of Biochemistry at the Institute of Medical Biochemistry, Federal University of Rio de Janeiro and a member of the research team.

 

ADDLs bound to synapses remove insulin receptors from nerve cells, rendering those neurons insulin resistant, William Klein, senior author and professor of neurobiology and physiology at Northwestern’s Cognitive Neurology and Alzheimer’s Disease Center, and colleagues showed in related work. The study’s authors surmised the outcome of the molecular-level battle between ADDLs and insulin, which in the current study was found to remove ADDL receptors, may determine whether a person develops Alzheimer’s disease.

 

Developing diabetes before the age of 65 was associated with a 125 percent increased risk of subsequently developing Alzheimer’s disease, according to Dr. Margaret Gatz, a professor of psychology, gerontology and preventative medicine at the University of Southern California, who tracked rates of dementia and diabetes in Swedish twins. The study, which bolstered the link between diabetes and dementia, was published in the January 2009 issue of the journal Diabetes. .

 

Their research was the outcome of recent studies that have linked vascular risk factors to an increasing risk of vascular dementia and Alzheimer’s disease. They decided to focus on diabetes because vascular risk factors associated with the disease are potentially modifiable by changing health behavior.

 

The researchers found that diabetes was a risk factor for both vascular dementia and for Alzheimer’s disease, although the association was more robust for vascular dementia than for Alzheimer’s disease. They also discovered that diabetes that first occurred before age 65 was a far more important risk factor for dementia than diabetes that did not occur until after age 65.

 

They surmised that although diabetes could be a possible cause of dementia, it is also likely that diabetes and dementia each arise from the same environmental exposures and influences. For example, the same adverse early childhood conditions that lead to higher rates of diabetes (such as a low birth weight) may also affect brain development. They concluded that a complex interplay of genetic factors and environmental exposures throughout the entire life course likely affects risk of dementia in old age. Their results also suggested that age of diabetes onset, rather than how prolonged diabetes treatment had been, might be an important factor in later dementia risk.