A genetic study identifies the causes of migraine and

image: QUT genetics researchers Professor Dale Nyholt and Hamzeh Tanha.
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Credit: QUT

Genetics researchers at QUT have discovered blood proteins that cause migraines and have a common link with Alzheimer’s disease that could potentially be prevented by reorienting existing therapies.

The results of the genetic analyzes have been published in Nature Communication by Professor Dale Nyholt and his PhD student Hamzeh Tanha from the QUT Center for Genomics and Personalized Health.

Professor Nyholt said the study identified causal genetic links between migraine risk and altered levels of five blood proteins:

  • Lower levels of FARS2, GSTA4 and CHIC2 proteins linked to inflammation and migraine.
  • Higher levels of DKK1 and PDGFB proteins inhibit Wnt signaling pathways and have links to cerebral calcification disorders.
  • The risk-increasing effect of DKK1 provides a potential mechanistic link between previously reported associations between migraine, Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA).

Professor Nyholt said people with migraine had higher levels of DKK1 and PDGFB, and lower levels of FARS2, GSTA4 and CHIC2 which causally increased their risk of migraine.

He said higher levels of blood proteins DKK1 and PDGFB inhibit Wnt signaling pathways that transmit biological signals to cells and can lead to brain calcification as well as inflammation causing pain, while lower levels of proteins Blood antioxidants FARS2, GSTA4, and CHIC2 also caused migraine-related inflammation.

“Notably, our finding of a strong causal effect of higher levels of DKK1 on migraine risk may be related to reduced Wnt signaling as observed in Alzheimer’s disease and cerebral amyloid angiopathy,” said Professor Nyholt.

“Cerebral amyloid angiopathy is an accumulation of proteins in cerebral arteries known to cause Alzheimer’s disease and reduction in Wnt signaling has also been shown to increase neuropathic pain in a rat model.”

Professor Nyholt said migraine was one of the most common neurological diseases in the world and under-researched given its significant public health burden.

In Australia alone, he said the estimated cost to the Australian economy was around $35.7 billion a year and that current treatments failed up to 50% of migraine patients.

Professor Nyholt said proposed therapies for Alzheimer’s disease called Wnt activators that restore Wnt/beta-catenin signaling in the brain could represent new therapeutic tools for the treatment of migraine.

“The good news is that there is already some therapy development targeting DKK1 augmentation for the treatment of Alzheimer’s disease and the potential to redirect this therapy for migraine,” Professor Nyholt said.

Professor Nyholt said that while reorienting existing therapies also had the potential to prevent Alzheimer’s disease in some migraine patients, the solution was not so simple.

“There is no genetic link between migraine and Alzheimer’s disease but, in theory, controlling DKK1 levels could potentially prevent migraine sufferers from developing Alzheimer’s disease.

“However, although a subset of people with Alzheimer’s disease may also have a history of migraine, not all migraine patients will have this connection – not all people with migraine will develop Alzheimer’s disease. Alzheimer’s.

“There is usually no single cause for these complex conditions leading to diagnosis. There are many different mechanistic pathways that can go wrong and lead to disease.

“Our results suggest that increased DKK1 protein production may be just one such biological mechanism underlying the reported increased risk of Alzheimer’s disease in migraine patients.”

Professor Nyholt said most genes contain information used to produce proteins, essential molecules needed for the structure, function and regulation of tissues and organs in the body.

He said alterations in blood proteins are promising diagnostic biomarkers and therapeutic targets because those secreted by multiple tissues and cell types may be associated with disease through shared biological processes.

Professor Nyholt said that future clinical studies should examine whether altering the blood levels of the proteins involved, such as the use of DKK1 inhibitors currently available or being studied, reduces the onset of migraine in patients. migraine.

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