A new molecular study reveals for the first time that high blood sugar or glucose damages an important enzyme that is involved with how the immune system responds in the early stages of Alzheimer’s disease. The researchers say the findings will help map the progression of the devastating disease to better identify those at risk and perhaps find new ways to treat or prevent it.

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Many experts believe the damage to brain cells caused by Alzheimer’s disease starts 10 years or more before symptoms of mental decline appear.

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

However, apart from the fact that people with diabetes have a higher risk of developing Alzheimer’s disease, the link between hyperglycemia and this common cause of dementia has been less clear.

Now, researchers show that macrophage migration inhibitory factor (MIF) – an enzyme that plays an important role in immune function and insulin regulation – undergoes damage associated with high glucose in early Alzheimer’s disease.

The team – from the University of Bath and King’s College London, both in the United Kingdom – describes the findings in a paper published in the journal Scientific Reports.

Alzheimer’s is a progressive brain-wasting disease that erodes people’s ability to remember, think, perform daily tasks, and lead an independent life.

Fast facts about Alzheimer’s disease
  • Experts suggest there are more than 5 million people with Alzheimer’s disease in the United States.
  • The first symptoms of the disease vary from person to person.
  • Genetic mutation is usually the cause of early-onset Alzheimer’s.

Learn more about Alzheimer’s

Among older adults, Alzheimer’s disease is the most common cause of dementia, a condition that affects 46 million people worldwide.

As more studies are done, scientists are gradually unraveling the complex changes that happen in the brain during the onset and development of the disease.

Many experts believe the damage caused by Alzheimer’s disease starts 10 years or more before the cognitive decline becomes apparent.

During this preclinical stage, when people appear symptom-free, toxic changes are taking place in the brain.

One of the main changes occurring in the brain is the accumulation of abnormal proteins into toxic plaques and tangles, causing once-healthy cells to stop working, lose connections with other cells, and die.

Scientists already knew that glucose and its metabolic byproducts can damage proteins through a reaction called glycation, which has also been linked to Alzheimer’s disease, and is a known feature of the hyperglycemia induced by diabetes.

For the new study, the researchers used a sensitive technique to detect glycation in brain samples from people with and without Alzheimer’s disease.

The team found evidence that the enzyme MIF undergoes glycation damage in the early stages of the disease. It also seems that the extent of MIF glycation increases as the disease progresses.

MIF is involved in how brain cells called glia respond to the buildup of the abnormal proteins during Alzheimer’s disease.

The team suggests that sugar damage to MIF reduces some of the enzyme’s functions and blocks others completely, and this could be the “tipping point” that allows Alzheimer’s to develop.

“We’ve shown that this enzyme is already modified by glucose in the brains of individuals at the early stages of Alzheimer’s disease,” says Jean van den Elsen, one of the senior investigators and professor in biology and biochemistry at Bath.

He and his colleagues are now investigating if they can detect similar changes in the blood.

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.”

First author Dr. Omar Kassaar, University of Bath

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