Second Alzheimer's gene identified: study
CHICAGO, AFP Friday, June 8, 2007, 12:00 am TWN
Researchers have identified a gene that dramatically increases a person's risk for developing Alzheimer's if they are already predisposed to this type of dementia, according to a study released Wednesday.
On its own, the gene variant, GAB2, appears to be benign, but when it's coupled with a variant of the APOE gene, the major genetic marker for the illness, it raises a person's chances of developing the degenerative condition four-fold.
Individuals with a copy of the APOE4 gene variant are four times more likely than the general population to develop late-onset Alzheimer's, a crippling neurological condition that progressively and irreversibly destroys a person's memory and cognitive function.
In people with both gene variants, the risk factor is 16 times greater. In theory, that genetic double-whammy could result in earlier onset of the disease and earlier death, one researcher said.
Investigators believe that the GAB2 variant boosts the effect of the APOE4 gene variant, by aggressively increasing the formation of tangles, one of the two proteins that clog up the brains of Alzheimer's patients.
"GAB2 acts like a dimmer switch or a volume button on APOE4," explained Dietrich Stephan, director of the neurogenomics division at the Translational Genomics Research Institute (TGen) in Phoenix, Arizona.
The researchers identified the gene by screening the DNA of 1,400 people, half of whom had Alzheimer's disease or AD.
In separate laboratory experiments, they showed that "silencing" the gene in human brain cells led to in an increase in the formation of a key protein that contributes to the tangles that destroy brain cells in the millions of elderly people afflicted with the malady.
Based on these findings, and previous research, the researchers believe that GAB2 might function under normal conditions to compensate for the harmful effects of APOE4 in older people, but that the variant of this gene lacks the protective effect.
If that finding is confirmed, the discovery could provide a target for future AD drugs.
"We hope that this study will contribute to the clarification of Alzheimer's risk factors and disease mechanisms, the discovery of promising new disease-slowing and prevention therapies, and the identification of patients and at-risk people most likely to benefit from those treatments," said Eric Reiman, lead author on the paper.
Reiman is executive director of the Banner's Alzheimer's Institute in Phoenix, Arizona — one of 15 institutions that collaborated on this study.
An estimated 28 million people have AD worldwide and experts predict that number will escalate sharply in the coming years as the number of elderly people as a percentage of the global population increases, but effective therapies are lacking. The study is published in the journal Neuron. The Mayo Clinic in Arizona, the Netherlands Brain Bank and the Alzheimer's Disease Centers of the National Institutes of Health in the United States participated in the project.
In a separate study, researchers at Massachusetts General Hospital in Charlestown, said they have identified the process by which strokes and head injuries put a person at greater risk of developing Alzheimer's disease.
The team said that the cell death caused by a brain injury such as a stroke or head injury enhances formation of brain-clogging amyloid plaques by means of a molecular chain reaction.
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