By Shana SagerThe Daily Northwestern

When they begin to lose the ability to remember words, many people assume they have Alzheimer’s disease. But they might have primary progressive aphasia, a disorder that impairs the ability to understand speech and use language.

Feinberg School of Medicine researcher Marsel Mesulam discovered the disease in 1982. Now, he and his colleagues have found its genetic cause – a discovery that might lead to better treatment for the rare condition.

Although primary progressive aphasia is rarely genetic, researchers identified a gene mutation in two unrelated families with siblings who have the disorder. In both families, the siblings with PPA had the mutation while the unaffected individuals did not.

“Once you have a genetic mutation, it gives you a molecular clue that you can use to clarify the underlying causes of the disease,” said Mesulam, director of Feinberg’s Cognitive Neurology and Alzheimer’s Disease Center.

Researchers also found that the mutation is different from those that cause Alzheimer’s, as the PPA mutation takes place in progranulin genes.

“Genes that cause Alzheimer’s lead to a buildup of something toxic in the brain,” Mesulam said. “The goal in therapy is to remove that toxic substance.”

The progranulin mutation, however, leads to a deficiency of progranulin.

“This raises the possibility that treatment here may be a little less challenging by replenishing progranulin,” he said.

According to Feinberg Prof. Sandra Weintraub, director of the clinical core of the Alzheimer’s Disease Center, this discovery can help researchers approach PPA treatment.

“Unless you can link it to some kind of genetic marker, it is very difficult to know what kind of protein abnormalities are being produced in the brain,” Weintraub said. “This is the first time that a language-specific loss of function has been linked to a gene.”

This genetic link enables researchers to explore how and why the disease seems to recognize the part of the brain that deals with language, she said.

Weintraub said about six cases of PPA are reported each month. Most people with its symptoms have been previously diagnosed as having Alzheimer’s or a stroke and are now returning for a second opinion, she said.

Mesulam estimates the disorder affects tens of thousands of people.

While Alzheimer’s usually at age 70 or after, patients with PPA are diagnosed in their 50s and 60s. The early onset of the disease is shocking to many, said Jennifer Medina, a Feinberg graduate student.

Medina serves as a coordinator for the school’s Frontotemporal Dementia/PPA Caregiver Education and Support Program. The group offers information and guidance for patients with PPA and their families.

“People are leading active lifestyles, and they aren’t expecting to be diagnosed with dementia,” she added.

The disease takes on different symptoms in each patient. Some people are able to speak fluently, but they lose their understanding of what words mean.

Others are able to remember the meaning of important words but lose the ability to form whole sentences. Regardless, people with PPA recognize their loss of language as the disease progresses, even if they cannot express what it means to them.

People with PPA have their memories intact and can still cook and do other hobbies, Medina said.

“(But) they can’t read a book anymore, give a lecture or have a conversation,” she said.

Reach Shana Sager at [email protected].