3rd Gene Find Raises Hopes About Alzheimer's

In a discovery that researchers hope will lead to new treatmentsfor Alzheimer's disease, scientists have found the third - and whatthey believe to be the last - defective gene that causes an inheritedform of the disabling neurological illness.

The new gene, reported in today's edition of the journalScience, is particularly important, scientists say, because it issimilar to another Alzheimer's gene identified six weeks ago.

The discovery of two nearly identical genes that cause the samedisease is virtually unprecedented, scientists said, and stronglysuggests that they play a crucial role in the onset of the disorder.

"It is extremely important that the new gene" is similar to apreviously discovered gene and that the proteins they produce arealso similar, said neuroscientist Dennis Selkoe of Harvard MedicalSchool, who was not involved in the research.

The existence of two distinct but very similar genes that causethe disease suggests that the genes, or others like them, play acrucial role in other forms of the disease as well, he said.

Inherited Alzheimer's, which strikes victims in their 40s - 10to 20 years earlier than noninherited Alzheimer's - accounts for asmuch as 10 percent of the 4 million cases of Alzheimer's amongAmericans.

The research team, headquartered at the University ofWashington, also believes it is the final gene that is responsiblefor inherited Alzheimer's and that its discovery will allow them tobetter understand the disorder.

"This is an incredibly important discovery," said neurologistMarcelle Morrison-Bogorad of the University of Texas, SouthwesternMedical School in Dallas, a member of the Alzheimer's Association'sMedical and Scientific Advisory Board. "This means that genetics haspretty much solved the mystery of early-onset Alzheimer's disease,and it clears the path for scientific research that wasn't therebefore."

Researchers are now working to figure out the exact function ofthe two proteins produced by the two genes and how that function isaltered by mutations. And if they are successful, experts believethey can quickly find drugs that will restore normal activity of theprotein and prevent the progression of Alzheimer's.

"If we can figure out what (the protein) is normally doing andwhy (this) mutation . . . can lead to Alzheimer's, we've gotsomething big on our hands," said neuroscientist Creighton Phelps ofthe National Institute of Aging, which funded the research.

"Our knowledge of the molecular culprits in the disease has justincreased dramatically," said David J. Galas of the Darwin MolecularCorp. in Seattle, which identified the mutation in the gene.

The new gene, called STM2, was isolated from a small set ofclosely related families called the Volga Germans. They aredescendants of a small group of Germans who settled along the VolgaRiver in Russia in the 18th century and then migrated to the UnitedStates earlier this century. The families have a very high incidenceof inherited Alzheimer's, which strikes early in life and progressesmuch more rapidly than the noninherited form.

Neuroscientist Gerard Schellenberg and his colleagues at theVeterans Affairs Medical Center and the University of Washington,both in Seattle, have been studying the Volga Germans for more than adecade.

Researchers said they believe they have identified all of thegenes for inherited Alzheimer's. All of the known families withinherited Alzheimer's have a defect in one of the three genes thathave been identified.

How these genes relate to the 90 percent of Alzheimer's casesthat are not inherited is still a mystery. Researchers have not yetreported finding any sporadic cases in which the genes are mutated,but they have only just begun looking. Some say there may be other,similar genes, as well.