NEW ALZHEIMER'S CANDIDATE GENE
Henahan, Access Excellence
A gene identified in an extended German family with a high
prevalence of Alzheimer's disease adds an important piece to the
research puzzle, report researchers.
The study began with an analysis of a familial group known
as the Volga German (VG) kindreds, a group of related families
with ties to Germany, Russia and the United States. The families
in the group emigrated from Germany to an area in Russia in the
18th Century and then came to the United States earlier this
century. Members of this group were observed to be at much
higher than average risk for early-onset Alzheimer's disease, a
type which develops before age 65.
A series of genetic studies produced a candidate gene on
chromosome 1, called STM2. The chromosome 1 STM2 protein
sequence resembles that observed in another gene localized on
chromosome 14 earlier this year. Researchers have also
previously identified a gene associated with Alzheimer's disease
on chromosome 21.
"We are very excited by the discovery of this new
Alzheimer's gene-- it opens new scientific avenues to
researchers," said Gerard D. Schellenberg, Ph.D., Associate
Director For Research, Seattle VA Medical Center.
The newly discovered mutation of STM-2 is quite rare, but
the new gene may code for an unknown protein that is part of the
poorly understood process leading to Alzheimer's disease in all
patients. Some 70 percent of patients with early-onset
Alzheimer's disease have the chromosome 14 defect, while the
defect in chromosome is found in about 25 percent of cases. The
chromosome 21 mutation is seen in approximately five percent.
"Finding out the function of the protein made by this gene
and how that function is altered when the gene is mutated has
great potential consequences for developing new therapies that
could help all Alzheimer's patients," said Rudolph Tanzi, Ph.D.,
Director of the Massachusetts General Hospital Genetics and
Aging Unit, Boston, MA.
The discovery of this gene gives researchers an important
new clue towards a better understanding of what causes the
formation of amyloid-beta, a toxic substance found in the
brains of patients with Alzheimer's. Determining the function of
the proteins associated with the three Alzheimer's genes should
help researchers develop a drug to slow or stop the disease
"Discovery of this gene probably completes the roster of
genetic causes for inherited early onset Alzheimer's," said
Wilma Wasco, Ph.D., a member of the MGH team. Dr. Tanzi added,
"Every new gene and mutation that we find brings us closer to an
effective treatment, and maybe a prevention, for this
Adds Dr. Schellenberg, "Genetics has proven to be the most
powerful tool by far for understanding diseases like this one.
Though we still have a long way to go to find a cure,
identifying this new Alzheimer's gene allows us to `connect the
dots' -- so to speak -- to earlier discoveries made in this
Alzheimer's disease is a progressive, degenerative disease
of the brain that results in impaired memory and dementia.
Alzheimer's disease, named for Alois Alzheimer, the German
neurologist who first described the pathology of the disease
nearly 100 years ago, is the fourth leading cause of death in
the developed world, after heart disease, cancer, and stroke.
Alzheimer's disease costs the nation nearly $60 billion/year.
"The great news is that we have located the genetic
mutations that account for almost all families with early-onset
familial Alzheimer's,'' said Leonard Berg, M.D., chair of the
Alzheimer's Association's Medical and Scientific Advisory
Board. "`We're much further ahead than we were even four years
ago. The difficult task ahead is to find the steps between
mutation and disease, and then identify those we can address
through intervention,'' said Berg, professor of neurology and
director of the Alzheimer's Disease Research Center at
Washington University in St. Louis. "The task is difficult
because it is likely that none of the known mutations acts
alone. They may be impacted by a number of genetic and
The current research, a collaborative effort among
scientists at the Seattle Veteran's Affairs Medical Center's
Geriatric Research Education and Clinical Center, the
Massachusetts General Hospital, and Darwin Molecular
Corporation, is reported in the Aug. 18, '95 issue of Science.
Related information on the
Institute for Brain
Aging and Dementia