Migraine risk linked with blood protein levels

Genetic researchers at the Queensland University of Technology (QUT) have found several blood proteins that cause migraine and have a shared link with Alzheimer’s disease, which could potentially be targeted by repurposing existing therapeutics. Their findings were published in the journal Nature Communications.

Study leader Professor Dale Nyholt said the research identified causal genetic links between migraine risk and altered levels of five blood proteins. People with migraine had higher levels of DKK1 and PDGFB, and lower levels of FARS2, GSTA4 and CHIC2 that causally increased their risk of migraine.

He said higher levels of DKK1 and PDGFB blood proteins inhibited Wnt signalling pathways that pass biological signals into cells and could lead to brain calcification as well as inflammation causing pain. Lower levels of the antioxidant blood proteins FARS2, GSTA4 and CHIC2 also caused inflammation linked to migraine.

“Notably, our finding of a strong causal effect of higher levels of DKK1 on migraine risk might be linked to a reduction in Wnt signalling as observed in Alzheimer’s disease and cerebral amyloid angiopathy,” Nyholt said.

“Cerebral amyloid angiopathy is a build-up of proteins in brain arteries known to cause Alzheimer’s disease and reduced Wnt signalling has also been shown to increase neuropathic pain in a rat model.”

Nyholt said therapies proposed for Alzheimer’s disease called Wnt activators that restore Wnt/beta-catenin signalling in the brain could represent novel therapeutic tools for migraine treatment, which would be helpful given that current treatments fail up to 50% of migraine patients.

“The good news is that there is already some development of therapy targeting increased DKK1 for Alzheimer’s treatment and potential to repurpose that therapy for migraine,” Nyholt said. He added that while repurposing existing therapies has the potential to prevent Alzheimer’s in some migraine patients, the solution is not that simple.

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

“However, although a subset of individuals who have Alzheimer’s may also have a history of migraine, not all migraine patients will have this link — not all people with migraine will get Alzheimer’s disease.

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

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

Nyholt said most genes contain information used to produce proteins — critical molecules required for the structure, function and regulation of the body’s tissues and organs. He said alterations in blood proteins are promising diagnostic biomarkers and therapeutic targets because those secreted from multiple tissues and cell types may be associated with disease via shared biological processes.

Nyholt said future clinical studies should examine whether altering blood levels of the implicated proteins, such as using DKK1 inhibitors currently available or under study, reduces migraine occurrence in migraine patients.

Image credit: ©stock.adobe.com/au/Laurin Rinder

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