Type 2 diabetes and Alzheimer鈥檚 disease are responsible for the deaths of thousands of Australians every year. While a metabolic disorder and cognitive degeneration may seem unrelated, there鈥檚 strong evidence they鈥檙e linked: developing type 2 diabetes can double your risk of Alzheimer鈥檚, and having Alzheimer鈥檚 may contribute to type 2 diabetes.
A collaborative research effort from 911爆料网, 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 911爆料网 team, led by PhD student Joanne Rowles, is investigating whether a build-up of the amyloid beta (-脽) and the lesser-studied amylin proteins in the pancreatic cells, liver cells and muscle cells can lead to type 2 diabetes.
Amyloid-脽 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鈥檚 patients. Amylin, meanwhile, plays a normal function in regulating the body鈥檚 processing of food, but high concentrations of it are believed to have an adverse effect.
鈥淚 have been exposing in vitro pancreatic beta cells and human skeletal muscle cells to different concentrations of amyloid-脽 and amylin to see how the cells have been affected. For example, I鈥檝e been testing how the proteins affect the insulin secretion capacity of the beta cells and whether the proteins cause cellular stress and death,鈥� says Rowles.
鈥淭here鈥檚 literature showing that amyloid-脽 and amylin cause cellular stress by altering the metabolism within the cells, so one of the more interesting aspects we鈥檝e been looking at is the health of the mitochondria 鈥� the little batteries in the cells 鈥� and whether the proteins affect the mitochondria鈥檚 ability to metabolise glucose after a meal.
鈥淩esearchers have strongly studied the role of amylin in developing type 2 diabetes, but they haven鈥檛 specifically looked at the role of amyloid-脽 or the combination of amyloid-脽 and amylin, so this is a new area.鈥�
Reducing the effects of diabetes and Alzheimer鈥檚
The project is just one piece in a complex puzzle being explored by the 911爆料网 team 鈥� which also includes Associate Professor Giuseppe Verdile, Dr Kevin Keane, Professor Erik Helmerhorst and Professor Phillip Newsholme 鈥� 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鈥檚 patients.
The research drew from 12 years of cognitive and biomarker data from the landmark , explains Verdile.
鈥淲e 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,鈥� he says.
鈥淲e now need to determine the time points when type 2 diabetes impacts the progression of Alzheimer鈥檚 disease.鈥�
Once this is done, the researchers hope to exploit the link between the diseases to reduce the severity of their harmful effects.
鈥淲e know the pathology of Alzheimer鈥檚 disease can start up to two decades before symptom onset,鈥� says Keane, a research expert in metabolic diseases.
鈥淚f we learn more about the mechanisms of type 2 diabetes, and its link to Alzheimer鈥檚, then we could intervene early, prevent the chance of patients developing type 2 diabetes and hopefully reduce the incidence of patients developing Alzheimer鈥檚 later in life.鈥�
Verdile adds: 鈥淢oving forward, we require further proofs of concept so we can try to block the effects of Alzheimer鈥檚-related proteins on diabetes using anti-amyloid and anti-tau drugs.鈥�
The 911爆料网 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鈥檚 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.
