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Home » Researchers Discover Genetic Cause of Word-Finding Disease
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Researchers Discover Genetic Cause of Word-Finding Disease

By medwebJan 1, 2007
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January 15, 2007

Contact: Marla Paul at (312) 503-8928 or at
marla-paul@northwestern.edu

Researchers Discover Genetic Cause of Word-Finding Disease

CHICAGO—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 (PPA), 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 M.-Marsel Mesulam, MD, lead author of the study and Ruth and Evelyn Dunbar Distinguished Professor of Neurology and professor of psychiatry and behavioral sciences at Northwestern University’s Feinberg School of Medicine. Dr. 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 forties and fifties.

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 of four siblings had the disease; in the second family, two 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 the January issue of Archives of Neurology and was the subject of an editorial in the journal.

“We’re dealing with one of the most puzzling phenomenons in neurology,” said Dr. 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 also the uniquely identifying features of human language. That’s a pretty big question,” added Dr. Mesulam.

Magnetic resonance 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 sculpting and one kept up her organic garden. We have patients who do very complicated things even when they can’t put two sentences together,” Dr. Mesulam said. Alzheimer’s patients lose interest in their hobbies and family life, he noted.

As PPA progresses during a 10–15 year period, however, patients eventually lose their ability to function independently.

The study was supported by grants from the Alzheimer’s Disease Core Center, Alzheimer’s Disease Coordinating Center, Alzheimer’s Disease Research Center, National Institute on Aging, and Association for Frontotemporal Dementia.

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