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Scientists pinpoint blood sugar-Alzheimer's 'tipping point'

Scientists have established a "tipping point" link between the blood sugar glucose and Alzheimer's disease.

Research from the University of Bath found excess glucose damages a vital enzyme involved with inflammation response to the early stage of the disease.

Abnormally high blood sugar levels, or hyperglycaemia, is a well-known characteristic of diabetes and obesity.

Diabetes patients have an increased risk of developing Alzheimer's, where abnormal proteins aggregate to form plaque and tangles in the brain.

It was already known that glucose and its breakdown products can damage proteins in cells through a reaction called glycation.

Scientists have now unravelled the specific molecular link between glucose and Alzheimer's disease.

They found that, in the early stages of Alzheimer's, glycation damages an enzyme called MIF (macrophage migration inhibitory factor).

MIF, which plays a role in immune response and insulin regulation, is involved in the response of brain cells called glia to the build up of abnormal proteins in the brain during the disease.

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 the disease progresses, the glycation of these enzymes increases.

Professor Jean van den Elsen, from the University of Bath's department of biology and biochemistry, said: "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."

In the study, scientists from the university worked with colleagues at the Wolfson Centre for Age Related Diseases, King's College London.

They studied brain samples from people with and without Alzheimer's disease, using a sensitive technique to detect glycation.

The work is published in the journal Scientific Reports.

Dr Rob Williams, also from the department of biology and biochemistry, added: "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."

Globally, there are around 50 million people with Alzheimer's disease and the figure is predicted to rise to more than 125 million by 2050.

Dr Omar Kassaar, from the University of Bath, added: "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."

The study, funded by the Dunhill Medical Trust, used brain tissue provided through Brains for Dementia, a joint initiative between Alzheimer's Society and Alzheimer's Research UK in association with the Medical Research Council.

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