Neurology

Diabetes drugs may be useful for Alzheimer's, mice research finds

"Drugs prescribed to treat diabetes could cure Alzheimer's disease" is the significantly over-hyped headline in The Daily Telegraph.

What this new research actually found is that there seem to be shared biological processes between Alzheimer's and diabetes. But the study concerned did not look at treatments for the disease, never mind any possible cures.

The report highlights a study in genetically engineered mice concerning a human enzyme (BACE1) that is closely linked to the development of Alzheimer's disease in humans, and which recent studies have also shown could be linked to type 2 diabetes. This study supported this concept, finding that mice bred to produce BACE1 showed signs of poor glucose control when compared with "normal" mice.

Research has previously linked diabetes with the risk of getting Alzheimer's disease. Researchers now suspect the link also works the other way round, so people with Alzheimer's disease may be more likely to get diabetes after getting dementia.

This animal study therefore looked at potential mechanisms that might affect the development of both diseases. However, the findings may not necessarily translate to humans. It has not tested the effects of diabetes drugs on the signs and symptoms of Alzheimer's, or vice versa.

Much more research is needed. Talk of a treatment or cure for Alzheimer's is premature and risks getting people's hopes up unfairly.

Maintaining a healthy weight and eating a nutritious diet can reduce both the risks of type 2 diabetes and Alzheimer's, but as of yet, there is no guaranteed method to prevent Alzheimer's disease.

Where did the story come from?

The study was carried out by researchers from the University of Aberdeen and the University of the Highlands and Islands, and was funded by a variety of grants and fellowships from organisations including Romex Oilfield Chemicals, Scottish Alzheimer's Research UK, the University of Aberdeen, the British Heart Foundation, Diabetes UK and Study of Diabetes/Lilly.

The study was published in the peer-reviewed journal Diabetologia on an open-access basis, so it is free to read online.

The UK media seems to have jumped the gun, from a study that looks at complex metabolic pathways in genetically modified mice, to reports that diabetes drugs could cure Alzheimer's disease. The Daily Mail probably did the best job of covering it, although the first mention that the study was on mice came some way down the story.

The Daily Telegraph did a poorer job, with a headline that was entirely inappropriate for the implications of the study.

What kind of research was this?

This was an observational laboratory study of mice bred to produce a human enzyme called BACE1. The researchers compared the mice with wild-type ("normal") mice, looking at their glucose control, lipids (fats) and other indicators of diabetes. They wanted to see whether mice bred to produce BACE1 were more likely to show signs of diabetes.

BACE1 is linked to the production of amyloid protein in the brain, which is characteristic of Alzheimer's disease. Recent studies have also shown that a lack of this enzyme could protect against obesity and diabetes, suggesting it may have an influence on glucose regulation in the body.

Animal studies are useful ways of carrying out experiments that cannot be done on humans, but it is not certain that results in animals translate to results in humans or lead to new treatment approaches.

What did the research involve?

Researchers took two groups of mice – one group similar to mice found in the wild, and the other bred to express a human enzyme called BACE1 in their brain cells. They monitored and tested them at three, four, five and eight months of age. They compared the results between the two groups.

The mice had a range of tests, including for glucose tolerance and insulin production, CT scans to look at the amount of fat they had, and tests for a range of markers, including leptin (a hormone linked to hunger), glycogen (the form in which the liver stores glucose) and types of lipids.

The researchers used statistical analysis to compare results between the two groups of mice, taking account of their initial body weight and food consumption.

What were the basic results?

Mice with BACE1 had results similar to wild-type mice until they were about four months old. After that, their weight went down, but the amount of fat in their bodies went up.

Blood tests after four months showed raised glucose levels and progressive raised glucose intolerance, altered levels of hormones and lipids, impaired ability of the liver to store glucose as glycogen, and reduced metabolism of glucose in the brain. All of these results suggest the BACE1 mice were unable to control their glucose levels, which is the major sign of diabetes.

The researchers said their previous research had shown that BACE1 mice begin to show signs of dementia at four to six months of age. They added: "Our current findings therefore indicate that neuronal BACE1 induces global metabolic dysregulation, along with brain inflammation and amyloidosis-related cognitive decline." They say the study "pinpoints neuronal BACE1" as the major driver of the inability to regulate glucose.

How did the researchers interpret the results?

The researchers say they have demonstrated that "neuronal expression of human BACE1 causes systemic diabetic complications."

They say their work "provides insight into the complex mechanistic interactions between diabetes and Alzheimer's disease" and shows that not only does diabetes increase the risk of Alzheimer's disease, but that the reverse may also apply.

Conclusion

Both Alzheimer's disease and diabetes seem to have become more common in recent years, causing illness and putting strain on the health service. News that the two illnesses may have a common cause raises hopes that drugs which help with one disease may also be of use in treating another.

Trials of a diabetes drug on people with Alzheimer's disease are reported to be underway, although no results have been published yet. This study, suggesting a mechanism which may be involved in the early stages of both diseases, may increase the likelihood that common treatments will be useful.

The study's main limitation is that it was carried out on mice, and studies in animals do not always translate directly to people. It's important to realise the study was not looking at ways to cure either diabetes or Alzheimer's disease, but only at an enzyme which may be implicated in the development of both. We don't know exactly what effect it has on humans, or how many people with raised levels of BACE1 get diabetes or Alzheimer's.

Studies like these, carried out on laboratory animals, can play an important role in helping us discover more about diseases and their causes. But we won't know whether this insight will help to find a treatment for Alzheimer's disease until there have been human trials.

If you had been diagnosed with type 2 diabetes, then sticking to your recommended treatment plan, in terms of diet and medication, should help reduce your Alzheimer's risk. Read more about Alzheimer's disease prevention.


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