Fernanda De Felice at Queen's University has discovered a disease mechanism common to Alzheimer's disease and Type 2 Diabetes. This mechanism, which consists of a pathway leading to inflammation in different parts of the brain, leads to glucose intolerance, memory impairments, and degeneration of the connections between neurons, called synapses. This discovery can lead the way to new therapies to preserve brain health. These results were presented at the 2018 Canadian Neuroscience Meeting, in Vancouver.
‘Diabetes drugs can be effectively used to treat Alzheimer's disease symptoms and enhance brain health. Identifying the molecular links between Alzheimer's disease and diabetes can lead to the development of new therapeutic approaches based on anti-diabetic agents.’
Alzheimer's disease is a complex disorder. Health professionals and researchers are recognizing more and more that Alzheimer's disease affects more than just memory, as it also affects sleep, appetite, mood (often leading to depression). Compelling evidence indicates that brain regions not classically linked to memory are affected by this disease.
Alzheimer's disease and type 2 diabetes are both diseases whose prevalence is increasing worldwide. Studies have shown that Alzheimer's disease is a risk factor for type 2 diabetes, and vice-versa. Dr. De Felice and her team have therefore searched for common factors that could explain their co-occurrence.
"We know that the Alzheimer's brain responds less to insulin, which is also indicative of some form of cross-talk in the pathways of these diseases. By looking at non memory-related symptoms of Alzheimer's disease we are getting a better understanding of the complex nature of this disease and of the different pathways it affects " says Dr. De Felice.
Her research on models of Alzheimer's disease, both in mice and non-human primates, has led to the identification of a pathway that causes inflammation in the brain, and that affects insulin signaling and endoplasmic reticulum stress. Reduction in insulin or insulin signaling is responsible for the increased blood glucose levels seen in diabetes, while endoplasmic reticulum stress is a measure of cell damage, and can lead to cell death.
The molecular links between AD and diabetes suggest novel therapeutic strategies based on anti-diabetic agents. In previous work, Dr. De Felice's team had tested such a strategy, with the diabetes drug liraglutide. Her studies had shown that the drug could reverse cognitive impairment, changes in insulin sensitivity and restore synapses in non-human primate models of Alzheimer's disease.
"A better understanding of the pathway involved in the development of the complex symptoms of Alzheimer's disease will be key to identifying more therapeutic targets to treat this devastating disease, and preserve brain health," says De Felice.