A molecular “tipping point” that could explain sugar’s ties to Alzheimer’s disease has been identified by a group of U.K. researchers. The team has demonstrated that excess glucose damages a vital enzyme involved with inflammation response to the early stages of Alzheimer’s.
It is already known that abnormally high blood sugar levels, or hyperglycaemia, is a characteristic of diabetes and obesity, but its link to Alzheimer’s disease is less familiar.
Alzheimer’s disease is a condition in which abnormal proteins aggregate to form plaques and tangles in the brain, which then progressively damage the brain and lead to severe cognitive decline. Alzheimer’s is now the sixth-leading cause of death in the U.S..
Macrophage Migration Inhibitory Factor
By investigating brain samples from people with and without Alzheimer’s, using a sensitive technique to detect glycation, the team discovered that in the early stages of Alzheimer’s glycation damages an enzyme called macrophage migration inhibitory factor (MIF), which plays a role in immune response and insulin regulation.
Scientists already knew that glucose and its break-down products can damage proteins in cells via a reaction called glycation but the specific molecular link between glucose and Alzheimer’s was not understood.
Professor Jean van den Elsen, from the University of Bath Department of Biology and Biochemistry, explained:
“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. 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."
MIF is involved in the response of brain cells called glia to the build-up of abnormal proteins in the brain during Alzheimer’s disease, and the researchers believe that inhibition and reduction of MIF activity caused by glycation could be the ’tipping point’ in disease progression. It appears that as Alzheimer’s progresses, glycation of these enzymes increases.
Globally there are around 50 million people with Alzheimer’s disease, and this figure is predicted to rise to more than 125 million by 2050. The global social cost of the disease runs into the hundreds of billions of dollars as alongside medical care patients require social care because of the cognitive effects of the disease.
The study was funded by the Dunhill Medical Trust.
Omar Kassaar, Marta Pereira Morais, Suying Xu, Emily L. Adam, Rosemary C. Chamberlain, Bryony Jenkins, Tony James, Paul T. Francis, Stephen Ward, Robert J. Williams & Jean van den Elsen Macrophage Migration Inhibitory Factor is subjected to glucose modification and oxidation in Alzheimer’s Disease Scientific Reports 7, Article number: 42874 (2017) doi:10.1038/srep42874