Type 2 diabetes and Alzheimer’s disease are responsible for the deaths of thousands of Australians every year. While a metabolic disorder and cognitive degeneration may seem unrelated, there’s strong evidence they’re linked: developing type 2 diabetes can double your risk of Alzheimer’s, and having Alzheimer’s may contribute to type 2 diabetes.
A collaborative research effort from Curtin University, the University of Toronto, Edith Cowan University (ECU) and Macquarie University is working towards understanding the mechanisms behind it all, which will greatly improve early intervention strategies for both diseases.
The Curtin team, led by PhD student Joanne Rowles, is investigating whether a build-up of the amyloid beta (-ß) and the lesser-studied amylin proteins in the pancreatic cells, liver cells and muscle cells can lead to type 2 diabetes.
Amyloid-ß represents just one of the commonalities between the two diseases, with the malicious protein being present in both the pancreata of type 2 diabetes patients and in the brains of Alzheimer’s patients. Amylin, meanwhile, plays a normal function in regulating the body’s processing of food, but high concentrations of it are believed to have an adverse effect.
“I have been exposing in vitro pancreatic beta cells and human skeletal muscle cells to different concentrations of amyloid-ß and amylin to see how the cells have been affected. For example, I’ve been testing how the proteins affect the insulin secretion capacity of the beta cells and whether the proteins cause cellular stress and death,” says Rowles.
“There’s literature showing that amyloid-ß and amylin cause cellular stress by altering the metabolism within the cells, so one of the more interesting aspects we’ve been looking at is the health of the mitochondria – the little batteries in the cells – and whether the proteins affect the mitochondria’s ability to metabolise glucose after a meal.
“Researchers have strongly studied the role of amylin in developing type 2 diabetes, but they haven’t specifically looked at the role of amyloid-ß or the combination of amyloid-ß and amylin, so this is a new area.”
Reducing the effects of diabetes and Alzheimer’s
The project is just one piece in a complex puzzle being explored by the Curtin team – which also includes Associate Professor Giuseppe Verdile, Dr Kevin Keane, Professor Erik Helmerhorst and Professor Phillip Newsholme – to learn more about the mechanisms of the two diseases, the link between them and how to reduce their effects. The team works closely with Professor Paul Fraser from the University of Toronto, Associate Professor Simon Laws and Dr Prashant Bharadwaj from ECU, and Professor Ralph Martins from ECU and Macquarie University.
As part of this extensive collaboration, the researchers recently investigated another commonality: the presence of insulin resistance in the brains of Alzheimer’s patients.
The research drew from 12 years of cognitive and biomarker data from the landmark Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing, explains Verdile.
“We determined that increases in insulin resistance are associated with reductions in cognitive performance and verbal memory, so the ability to recollect and to make decisions. It is also associated with an increase in abnormal tau, a molecule that causes neuronal death,” he says.
“We now need to determine the time points when type 2 diabetes impacts the progression of Alzheimer’s disease.”
Once this is done, the researchers hope to exploit the link between the diseases to reduce the severity of their harmful effects.
“We know the pathology of Alzheimer’s disease can start up to two decades before symptom onset,” says Keane, a research expert in metabolic diseases.
“If we learn more about the mechanisms of type 2 diabetes, and its link to Alzheimer’s, then we could intervene early, prevent the chance of patients developing type 2 diabetes and hopefully reduce the incidence of patients developing Alzheimer’s later in life.”
Verdile adds: “Moving forward, we require further proofs of concept so we can try to block the effects of Alzheimer’s-related proteins on diabetes using anti-amyloid and anti-tau drugs.”
The Curtin research has been supported by funding from the WA Department of Health and the National Health and Medical Research Council.
The link between diabetes and Alzheimer’s and other types of dementia was first established in 1996 by Dutch researchers, who collected data on 6,330 individuals aged between 55 to 99 years old, as part of the ground-breaking Rotterdam Study.