Causal Genetic Connections Between Migraine Risk and Blood Proteins Have Been Identified

Causal Genetic Connections Between Migraine Risk and Blood Proteins Have Been Identified ...

Researchers at QUT have found blood proteins that cause migraine and have a shared connection to Alzheimers disease that might be avoided by repurposing existing therapies.

Professor Dale Nyholt and his PhD candidate Hamzeh Tanha from theQUT Centre for Genomics and Personalised Health published findings from genetic analyses in theNature Communications.

According to Professor Nyholt, the study investigated the causal genetic link 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 signalling pathways and have links to brain calcification disorders.
  • The risk-increasing effect of DKK1 provides a potential mechanistic link between the previously reported associations between migraine, Alzheimer''''s disease (AD), and cerebral amyloid angiopathy (CAA).

People with migraines had increased DKK1 and PDGFB, while low levels of FARS2, GSTA4, and CHIC2, causing their migraine risk to develop.

Higher levels of DKK1 and PDGFB blood proteins inhibited Wnt signalling pathways that transmit biological signals into cells, causing pain, and decreased levels of antioxidant blood proteins FARS2, GSTA4, and CHIC2 also caused inflammation.

Certainly, our finding of a strong causal effect of higher DKK1 on migraine risk may be linked to a reduction in Wnt signalling as seen in Alzheimers disease and cerebral amyloid angiopathy, according to Professor Nyholt.

A protein build-up in brain arteries that have caused Alzheimer''s disease and decreased Wnt signalling has been exhibited in a rat model.

Professor Nyholt said migraine is one of the world''s most widespread neurological diseases, and is under-researched in view of its significant public health burden.

The estimated cost to the Australian economy was $35.7 billion every year, but currently treatment failed to reach 50% of migraine patients.

Medications that have been proposed for Alzheimers disease, referred to as Wnt activators, that restored Wnt/beta-catenin signalling in the brain, might be effective for migraine treatment.

The good news is that there is already some development of therapy that focuses on increased DKK1 for Alzheimers treatment and the possibility of retrofitting that therapy for migraine, according to Professor Nyholt.

While repurposing existing therapies might help prevent Alzheimer in some migraine patients, Professor Nyholt claims that the solution wasn''t that simple.

There is no connection between migraine and Alzheimer''s disease, but in theory, controlling DKK1 levels might impede people from developing Alzheimer''s disease.

Despite the fact that a minority of people who have Alzheimers may have a history of migraine, not all migraine patients will have this connection. Alzheimers disease is not only affected by the disease, but also by the severity of the illness.

These complex conditions are often no single reason for diagnosis. There are many different mechanistic strategies that can go wrong and lead to illness.

Our findings suggest that an increase in production of the DKK1 protein might be just one of the most effective biological mechanisms to the basis of the reported increased Alzheimer''s disease risk in migraine patients.

Professor Nyholt said that the majority of genes contained information about proteins and crucial molecules that are required for the body''s structure, function, and regulation.

Modifications in blood proteins were effective diagnostic biomarkers and therapeutic targets, according to him, because those secreted from several tissues and cell types may be linked with disease through shared biological approaches.

Future clinical trials should examine whether altering blood levels of the implicated proteins, such as using DKK1 inhibitors currently available or under study, will reduce migraine occurrence.

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