The findings appear to centre on the damage high blood sugar levels does to a key enzyme in the inflammatory response in the condition’s early stages.
High blood sugar levels or hyperglycaemia is one of the hallmarks of diabetes as well as obesity and potentially places those with these conditions at a heightened risk of brain complications.
“Excess sugar is well known to be bad for us when it comes to diabetes and obesity, but this potential link with Alzheimer’s disease is yet another reason that we should be controlling our sugar intake in our diets,” said study author Dr Omar Kassaar, from the University of Bath.
In a joint collaboration involving scientists from the University of Bath and King’s College London, brain tissue from individuals with Alzheimer’s was studied.
The team were looking for evidence of glycation – a reaction that involves breaking down glucose into products that can damage proteins contained in cells.
The scientists noted that in the early stages of Alzheimer’s glycation played a major role in altering the function of an enzyme known as MIF (macrophage migration inhibitory factor) which mediates the immune response and regulates insulin levels.
More relevantly, MIF plays a role in preventing the build-up of abnormal proteins in the brain during Alzheimer’s disease.
The ‘tipping point’ in disease onset
It may be that inhibition of MIF’s role as a result of the glycation process may well be the ‘tipping point’ in disease progression.
The researchers believe the onset of Alzheimer’s is strongly linked with the glycation of these enzymes.
“We’ve shown that this enzyme is already modified by glucose in the brains of individuals at the early stages of Alzheimer’s disease. We are now investigating if we can detect similar changes in blood,” said Dr Jean van den Elsen, professor from the University of Bath’s Department of Biology and Biochemistry.
“Normally MIF would be part of the immune response to the build-up of abnormal proteins in the brain, and we think that because sugar damage reduces some MIF functions and completely inhibits others that this could be a tipping point that allows Alzheimer’s to develop.
Globally there are approximately 50 million people with Alzheimer’s disease, with this figure predicted to rise to over 125 million by 2050.
The global social cost of the disease runs into hundreds of billions of pounds in addition to medical care patients also need social care as a result of the cognitive decline the disease inflicts.
Metformin treatment clue
Despite the efforts made in mapping the progression of Alzheimer’s, the condition’s link to diet and especially sugar is not well understood.
It has been suggested that the prevalence of Alzheimer’s is increased in individuals with diabetes.
Even in individuals without diabetes, higher glucose levels have been associated with an increased incidence of the neurological condition.
Chronic inflammation, a common risk factor of diabetes and obesity, induced by the proinflammatory action of MIF is associated with insulin resistance and glucose intolerance.
In obesity, plasma MIF concentrations are increased, but treatment with the anti-diabetic and anti-glycation agent metformin, decreases the MIF levels to normal.
With this in mind the link between hyperglycaemia and dementia through glycation and inflammation becomes stronger.
“Knowing this will be vital to developing a chronology of how Alzheimer’s progresses and we hope will help us identify those at risk of Alzheimer’s and lead to new treatments or ways to prevent the disease,” said Dr Rob Williams, reader and study author based at the University of Bath’s Department of Biology and Biochemistry.
Source: Scientific Reports
Published online ahead of print: doi:10.1038/srep42874
“Macrophage Migration Inhibitory Factor is subjected to glucose modification and oxidation in Alzheimer’s Disease.”
Authors: Rob Williams, Omar Kassaar, Jean van den Elsen et al.