Spring 1996 Volume 5, Number 2
To date, three genes have been implicated. The first was found in 1987, but its mutations account for only 2 to 3 percent of FAD. Then, last summer, two new FAD genes were discovered. In June, an international team led by investigators at the University of Toronto announced a gene, presenilin 1 (PS1) on chromosome 14, that seems to be responsible for about 70 percent of early onset FAD. Weeks later, Rudolph Tanzi and Wilma Wasco at Massachusetts General Hospital, working with investigators in Seattle, discovered a similar gene, presenilin 2 (PS2), on chromosome 1.
As predictors of FAD, the presenilin genes will take a great deal of work: Already, they have shown 25 mutations associated with FAD, two in the PS2 gene, and 23 in the PS1 gene, and 17 of these are "private" mutations --occurring in single families and unlikely to show up in non-relatives.
Yet, PS1 and PS2 may tell an important story about nerve cell death in Alzheimer's. Researchers are intrigued by their similarity to two proteins in the nematode (a small worm much used in research). Tanzi and Wasco, basing their current studies on the nematode, recently found that, the presenilin-like proteins sit in the wrapping of tiny packets, called organelles, that transport essential molecules within cells. Tanzi believes that problems in the transport of proteins when presenilin genes are defective could provide valuable clues for blocking nerve cell death and preventing the loss of nerve-cell communication that takes place in AD.
