SYDNEY, May 13 (Xinhua) -- Australian researchers have found blood proteins that cause migraines and have a shared link with Alzheimer's disease that could potentially be prevented by repurposing existing therapeutics.
The research, published in Nature Communications and revealed to the public on Thursday, was conducted by researchers from the Queensland University of Technology (QUT). It utilized genome-wide association study (GWAS) statistics for blood levels of 4,625 proteins from six studies published between March 2016 and October 2020, and identified causal genetic links between migraine risk and five blood proteins.
Professor Dale Nyholt from the QUT Center for Genomics and Personalized Health said participants with migraine had higher levels of DKK1 and PDGFB blood proteins, and lower levels of FARS2, GSTA4 and CHIC2 that causally increased their risk of migraine.
Higher levels of blood proteins DKK1 and PDGFB inhibited pathways that pass biological signals into cells and could lead to brain calcification and inflammation, while lower levels of antioxidant FARS2, GSTA4 and CHIC2 also caused inflammation linked to migraine, said Nyholt.
Among the five proteins, the risk-increasing effect of DKK1 also provides a potential mechanistic link between the previously reported associations between migraines, Alzheimer's disease, and cerebral amyloid angiopathy.
"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 this means 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.
"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. ■