Yale researchers have made the first step in cracking the mystery of human dementia.

Since 2006, neurologists have been stumped by the role of a specific protein, progranulin, in the early stages of frontotemporal dementia. But in a paper published in the Nov. 18 edition of the scientific journal Neuron, Yale scientists determined part of the biological process that leads progranulin to cause this type of dementia. The disorder, which has historically been confused with Alzheimer’s Disease, currently has no known treatment and between 100,000 and 500,000 people live with the disease in the United States, according to the National Institute of Health’s Alzheimer’s Disease Education and Referral Center.

“There was zero information about what progranulin might do — no one knew what molecule was next in the pathway,” Yale neurology professor Stephen Strittmatter said.

The team found that the absence of a protein receptor called sortilin, which is found on the cell surface of neurons, can dramatically increase the amounts of progranulin in the brain.

This build-up of the protein is key to the development of frontotemporal dementia — a degenerative condition that affects the brain’s frontal and temporal lobes — but researchers do not yet understand exactly how this happens.

“We’ve identified the first step in the development of frontotemporal dementia,” researcher Thihan Padukkavidana GRD ’09 said. “It is still unclear exactly how this functioning works, though.”

Strittmatter and Padukkavidana said that while their study does not solve the entire mystery of how dementia transpires, it has several promising implications.

By understanding the first key step of the process with sortilin and progranulin, Strittmatter said many people around the world will be able to speed up their research in the field.

Padukkavidana said the receptor could provide a potential therapeutic avenue in the future, a notion that researchers at other institutions also find promising.

“This study opens up a whole new area of research on frontotemporal dementia,” said Eric Roberson, assistant neurology and neurobiology professor at the University of Alabama at Birmingham. “It is a major advance in understanding and potentially towards treating the disease.”

The study, which took place over two years in the United States, Vancouver and Denmark, was funded through the National Institutes of Health, the A.L.S. Association, the Falk Medical Research Trust and an anonymous donor.