Gene Variants and Alzheimer's Risk Potsdam NY

Two international teams of scientists have uncovered three gene variants that up the risk for Alzheimer's disease, the most common form of dementia among the elderly and the seventh-leading cause of death in the United States.

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SUNDAY, Sept. 6 (HealthDay News) -- Two international teams of scientists have uncovered three gene variants that up the risk for Alzheimer's disease, the most common form of dementia among the elderly and the seventh-leading cause of death in the United States.

Teams led by Dr. Philippe Amouyel of the Institut Pasteur de Lille in France, and Julie Williams, a professor of psychological medicine at Cardiff University School of Medicine in Wales, zeroed in on defects in the CLU, CR1 and PICALM genes, and also found another 13 gene variants that are solid candidates for further investigation, according to findings that appear in the Sept. 6 online issue of Nature Genetics. Until now, only four gene variants had previously been definitively associated with Alzheimer's -- APP, PS1, PS2 and APOE.

"Although the role of these two new genes [CLU and CR1] . . . is not yet known in detail, previous studies suggest that they may be involved in the elimination of the major component of amyloid plaques," explained Amouyel, the leader of the team that studied the CLU and CR1 genes. "Genetic variants at CLU, CR1 and APOE may influence susceptibility to late-onset forms of the disease."

According to Amouyel, one group of researchers carried out a two-stage analysis of genetic samples from more than 20,000 subjects. In parallel, Williams ran a similar study, discovering the PICALM gene mutations and independently discovering the CLU gene variants.

Most of the DNA samples came from France and other European countries, but U.S. labs contributed to Williams' study as well, including the National Institute on Aging (NIA) Laboratory of Neurogenetics, the Mayo Clinic and the Washington University School of Medicine in St. Louis.

"This is the most important finding in the genetic [component] of Alzheimer's in more than 10 years," said study co-author Alison Goate, a professor of genetics in psychiatry at Washington University School of Medicine and a member of the Alzheimer's Association Medical & Scientific Advisory Council.

Experts estimate that as many as 5.3 million Americans are living with Alzheimer's disease, which progressively kills brain cells. Alzheimer's typically attacks people over the age of 65. Symptoms include a range of cognitive, psychiatric and physical problems that eventually lead to death.

The sheer global impact of the illness and the lack of a cure were the driving forces behind the current research.

According to Amouyel, "the identification of these three genes has been possible, thanks to two major elements: first, the possibility to compare thousands of patients through a major collaboration between scientists; and second, the capacity to analyze genetic markers distributed all over the entire genome with high-tech tools, such as DNA chips."

Relatively little is known about how the newly discovered genes may increase the risk of Alzheimer's. But researchers have noted increased levels of CLU in the brains and cerebrospinal fluids of Alzheimer's patients. PICALM may play a role in the health of nerve cell synapses and may affect beta-amyloid deposits in the brain.

Each of the new genes probably contributes about 8 percent to an individual's risk of developing Alzheimer's, Goate said. In addition to genetic factors, there are likely to be environmental and lifestyle variables that also contribute to the risk, she noted.

"Identifying gene variants like CLU and PICALM advances our understanding of the many genetic factors that may contribute to overall risk for this devastating neurological disorder," Marcelle Morrison-Bogorad, associate director of NIA's neuroscience and neuropsychology of aging program, said in a statement. "This knowledge may then lead to novel disease pathways that can be targeted to develop new treatments."

In another genetic discovery reported in the same journal, Dutch researchers say they have found two new gene variants linked to amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. The variants appear to play a role in the neural pathways that are involved in this deadly disease, which involves the steady loss of neurons that results in muscle atrophy, paralysis and, finally, death.

More information

The Alzheimer's Association has more on the disease.

Author: By Peter West
HealthDay Reporter

SOURCE: Philippe Amouyel, M.D., Ph.D., Institut Pasteur de Lille, France; Alison Goate, professor, genetics in psychiatry, Washington University School of Medicine, and member, Medical & Scientific Advisory Council, Alzheimer's Association, Chicago; Sept. 6, 2009, Nature Genetics, online

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