Scientists said on Sunday they have pinpointed a new gene linked to Alzheimer’s disease, the incurable brain disorder that is the top cause of dementia in the elderly.
Abnormalities in a gene called SORL1 increased the risk for the disease, and this finding could help scientists develop new treatments, the researchers reported in the journal Nature Genetics.
The researchers looked at DNA samples from 6,000 people from four ethnic groups: Caribbean-Hispanics, North Europeans, black Americans and Israeli-Arabs. They found certain variations of SORL1 more often in people with late-onset Alzheimer’s disease than in healthy people.
The late-onset form, affecting people age 65 and up, represents about 90 percent of Alzheimer’s cases. The rarer early-onset form affects people from about age 30 to 65.
Only one other gene, called ApoE4, has been identified as a risk factor for late-onset Alzheimer’s. It was identified in 1993.
Several genes are linked with early Alzheimer’s, and study of both types might lead to better understanding of how the disease begins and how to tackle it.
Many scientists think Alzheimer’s begins with the buildup in the brain of a gooey material called amyloid that clumps together to form plaques. That material stems from a protein called amyloid precursor protein, or APP.
SORL1 controls the distribution of APP inside nerve cells of the brain. When working normally, the gene prevents APP from being degraded into a toxic byproduct called amyloid beta peptide. When SORL1 is deficient, it allows more of the bad amyloid beta peptide to accumulate, fostering amyloid plaques.
Alzheimer’s is a complex disease that gradually destroys a person’s memory and ability to learn, reason, make judgments, communicate and carry out daily activities. Scientists have struggled to understand the biology of the disease and its genetic and environmental causes.
‘PIECE OF THE PUZZLE’
"It’s another clue to the way in which this disease comes about, another piece of the puzzle," Dr. Peter St. George-Hyslop, director of the Center for Research in Neurodegenerative Diseases at the University of Toronto and one of the key researchers, said in a telephone interview.
"Every time you get a piece of the puzzle and you can relate it to something else in the puzzle, you’re that much closer to knowing what the picture on the puzzle is," he added.
St. George-Hyslop said it is premature to say what percentage of cases of late-onset Alzheimer’s disease can be attributed to SORL1. ApoE4, which also may be involved in the production of amyloid plaques, has been linked to about 20 percent of late-onset Alzheimer’s cases.
"This appears to be the fifth Alzheimer’s disease gene, and there are likely to be other important genetic variants that need to be identified before the entire picture is complete," Dr. Richard Mayeux of Columbia University Medical Center in New York, also involved in the research, said in a statement.
The disease first affects parts of the brain controlling memory and thinking, but as it advances it kills cells elsewhere in the brain. Eventually, if the patient has no other serious illness, the loss of brain function will prove fatal.
Researchers from Boston University and the Mayo Clinic College of Medicine in Jacksonville, Florida, also took part in the five-year study.