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Researchers discover genetic cause for word-finding disease

Northwestern University researchers have discovered a genetic cause of a mysterious neurological disease in which people have trouble recalling and using words. The illness, Primary Progressive Aphasia, differs from Alzheimer's Disease in which a person's memory becomes impaired. In PPA, a little known form of dementia, people lose the ability to express themselves and understand speech.

"This discovery, for the first time, provides a molecular approach to understanding the causes and eventually the treatment for this disease, " said Marsel Mesulam, M.D., lead author of the study and the Ruth and Evelyn Dunbar Professor of Neurology and Psychiatry at The Feinberg School of Medicine at Northwestern University. Mesulam was the first scientist to identify the word-finding disease in 1982. He estimated it affects tens of thousands of people, though no exact statistics are available. People can begin to show symptoms of PPA as early as in their 40's and 50's.

Scientists discovered the gene mutation, called a progranulin gene mutation, in two unrelated families in which nearly all the siblings suffered from PPA. In the first family, three out of four siblings had the disease; in the second family, two out of three had it. These particular mutations were not observed in the healthy siblings or in more than 200 control samples.

The study was published in January Archives of Neurology and is discussed in an editorial in the journal.

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"We're dealing with one of the most puzzling phenomenons in neurology," said Mesulam, director of Northwestern's Cognitive Neurology and Alzheimer's Disease Center. "Here is a disease that specifically attacks the language part of the brain on the left side. What makes it so specific? How does the disease target the language areas?"

"This finding will help us explore not just what causes the disease but the uniquely identifying features of human language. That's a pretty big question," added Mesulam.

MRI imaging of the brains of people with PPA shows the language part in the perisylvian region of the left hemisphere has shrunk. By comparison, Alzheimer's Disease targets the hippocampus on both sides of the brain.

One of the oddities about PPA is that even when people have lost their ability to speak, they are still able to maintain their hobbies and perform other tasks. "One of my patients redid his vacation home and rebuilt all the cabinets himself. Another took up sculpturing and one kept up her organic garden. We have patients who do very complicated things even when they can't put two sentences together," Mesulam said. Alzheimer's patients lose interest in their hobbies, family life and just sit doing nothing, he noted.

As PPA progresses over 10 to 15 years, however, patients eventually lose their ability to function independently.

Marla Paul | EurekAlert!
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