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For the first time a “tipping point” molecular link between the blood sugar glucose and Alzheimer’s disease has been established by scientists from the University of Bath and King’s College London in the UK.
They have shown that excess glucose damages a vital enzyme involved with inflammation response to the early stages of Alzheimer’s. Abnormally high blood sugar levels, or hyperglycaemia, is well-known as a characteristic of diabetes and obesity, but its link to Alzheimer’s disease is less familiar.
Diabetes patients have an increased risk of developing Alzheimer’s disease compared to healthy individuals.
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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.
By studying 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 MIF (macrophage migration inhibitory factor) which plays a role in immune response and insulin regulation.
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.
“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 Jean van den Elsen, from the University of Bath.
“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,” said van den Elsen.
“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 Rob Williams, from University of Bath.
“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 Omar Kassaar, from the University of Bath.