Study links diabetes drug target protein to reduced risk of Alzheimer’s disease


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The mechanisms associated with a specific diabetes drug could also help protect against Alzheimer’s disease, a study by researchers at Karolinska Institutet in Sweden published in Neurology reports. The results suggest that the drug’s target protein could be an interesting candidate for treating Alzheimer’s disease.

Alzheimer’s disease is becoming increasingly common, but there are no drugs that affect the course of the disease, and the development of new drugs is a slow, expensive and complex process.

Therefore, an alternative strategy is to find already approved drugs that can prove effective against the disease and give them a new field of application. Diabetes drugs have been put forward as potential candidates, but the studies that have been tested so far diabetic Alzheimer’s disease medications have not yielded convincing results.

In this study, researchers from Karolinska Institutet . used genetic methods To study this closely.

“Genetic variants within or near genes that encode drug target proteins can cause physiological changes similar to the drug’s effects,” says study first author Bowen Tang, a doctoral student in the Department of Epidemiology and Biostatistics, Karolinska Institutet. “We use such variables to test the potential for re-positioning already approved drugs.”

The researchers began by identifying genetic variants that mimic the pharmacological effect of diabetes drugsIt lowers the level of glucose in the blood. This was done by analyzing data from more than 300,000 participants in the UK Biobank registry.

The analysis identified variants in two genes that together code for a target protein of a class of diabetes drugs called sulfonylureas. The researchers validated these variables by showing their association with, among other phenomena, increased insulin secretion, a lower risk of type 2 diabetes, and a higher body mass index, which is consistent with the drug’s effects.

The researchers then examined the link between specific genetic variants and the risk of Alzheimer’s disease. They did this by analyzing data previously collected from more than 24,000 people with Alzheimer’s disease and 55,000 people from a control group. They found that genetic variants in the sulfonylurea genes are associated with a lower risk of Alzheimer’s disease.

“Our results suggest that a sulfonylurea target protein, KATP channel, may be a therapeutic target for the treatment and prevention of Alzheimer’s disease,” says Sarah Hag, an author of the latest study in the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. “This protein is expressed in the pancreas, but also in the brain, and more studies are needed to fully understand the basic biology.”

The method of analysis applied in the study is called Mendelian randomization, which uses knowledge of genetic variants in individuals as a kind of natural randomness, not different from randomization. Clinical study. Individuals born with certain protective variants that mimic the effect of a particular drug can thus be studied for their association with a disease.

Study identifies 11 candidate genetic variants of Alzheimer’s disease

more information:
Genetic variability in antidiabetic drug targets and Alzheimer’s disease risk–Mendel’s randomized study, Neurology (2022). doi: 10.1212/wnl.0000000000200771

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Karolinska Institute

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