A
research team
has found that a new test combining the effects of more than two dozen
genetic variants does a better job of predicting which cognitively
normal older adults will go on to develop Alzheimer's dementia.
The
advantage of the test, known as polygenic hazard score (PHS), is
relative to testing only for the well-known genetic variant APOE E4,
which has been considered the strongest genetic predictor of whether
someone is likely to develop Alzheimer's, a chronic neurodegenerative
disease that usually starts slowly and worsens over time.
However,
APOE E4 is only carried by 10 to 15 percent of the population and
recent research suggests its effects have been overstated.
Reporting
their findings this week in Annals of Neurology, the team led by
researchers at the University of California, San Francisco, or UCSF, and
the University of California, San Diego, believes that the PHS test
could provide risk estimates for the remaining 85 to 90 percent of
people who do not carry at least one copy of APOE E4 but still have some
combination of other genetic variants that put them at risk of
Alzheimer's.
By looking at five years of data on 1,081 subjects
from the U.S. National Alzheimer's Coordinating Center (NACC) who did
not have dementia, the researchers found that the PHS test could predict
how long it would take for them to progress to Alzheimer's dementia,
and how steep their cognitive decline would be.
The test enables
the researchers to calculate an age-specific risk of developing
Alzheimer's, based upon each person's share of 31 genetic variants, plus
APOE E4. It makes predictions by using genetic data from more than
70,000 people in the NACC database, the International Genomics of
Alzheimer's Disease Project and the Alzheimer's Disease Genetics
Consortium.
The Wall
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