The Frontier of Pathology

Indiana is the home of one of the few families in the world with a rare form of genetically transmitted Alzheimer's disease (see accompanying article). Oddly enough, there is a second family in the state with another extremely rare form of dementia known as Gerstmann-Straussler- Scheinker disease, or GSS for short. Dr. Ghetti learned of this family in 1977, and Farlow joined him in studying the family in 1985.

GSS is similar to Alzheimer's disease in some respects. Symptoms include gradual memory loss as well as gradual deterioration of other mental functions. GSS patients also have difficulty walking and coordinating movements. Their brains are characterized by amyloid plaques, tangles, and loss of neurons.

The amyloid in the brains of GSS patients, however, does not come from the beta-amyloid protein, as in Alzheimer's syndrome, but from a different protein, the prion protein. There are several other so-called prion diseases as well, such as Creutzfeld-Jakob disease. The fascinating thing about prion diseases is that, unlike any other known disease, some forms are genetic, some are infectious, and some are both. That is, at least some variants of the disease, including the Indiana variant, are the result of a mutation in the prion protein gene. But if tissue from a person with certain prion diseases is introduced into another person's body, that person may contract the disease. This has happened in several cases of Creutzfeld-Jakob disease through cornea transplants, for example. And in an extremely bizarre case, a prion disease called Kuru, found only in a particular tribe in New Guinea, was being transmitted through the practice of ritual cannibalism: tribespeople were contracting Kuru when they ate the brains of relatives who had died of the disease. Now that the cannibalism has stopped, the disease has virtually disappeared.

The mechanism by which prions infect people is unknown. As that mechanism begins to be understood, the resulting knowledge will most likely shed light not only on prion diseases, but also on more common neurodegenerative diseases such as Alzheimer's. "What we're hoping and finding," says Farlow, "is that by comparing Gerstmann-Strausslerr-Scheinker disease to Alzheimer's disease, we can better understand how particular symptoms we see in the diseases relate to particular pathologies in the brain."

So unusual are prions that their research may also contribute to an entirely new understanding of disease transmission in general.

--Mark Buechler