April 14, 2010 (Toronto) -- A newly identified gene appears to increase a
person’s risk of developing late-onset Alzheimer’s disease, the most common
type of Alzheimer’s disease.
People with a particular variation in the gene, dubbed MTHFD1L, may
be nearly twice as likely to develop Alzheimer’s disease as people without the
Still, the absolute risk of developing Alzheimer's will be "very small"
for any given individual that carries the variant, says Margaret Pericak-Vance,
PhD, director of the University of Miami Miller School of Medicine’s John P.
Hussman Institute for Human Genomics.
The study was presented at the annual meeting of the American Academy of
Gene May Explain 5% of Inherited Alzheimer's Disease
The search for new genes that predispose people to Alzheimer's disease has
been quite slow, Pericak-Vance tells WebMD.
It's been nearly two decades since researchers discovered the variants in
the ApoE gene that are associated with an increased risk for late-onset
Alzheimer's disease, which affects people 60 and older.
A mixture of genetic and environmental factors is thought to cause
late-onset Alzheimer's disease. About 60% to 80% of the disease is attributable
to genetics, and about 40% of that genetic effect is attributable to the ApoE4
MTHFD1L may help explain another 5% of inherited cases of the disease,
What makes this discovery "so exciting" is that the gene is known to be
involved in the metabolism of folate, which in turn influences the body’s
levels of homocysteine, she says.
High levels of homocysteine, which are associated with too little folate in
the diet, have been shown to be a
risk factor for Alzheimer’s disease, she says.
"A lot of the time we find a gene and have to figure out how it ties in to
the disease. This finding melds the genetics with the biology," Pericak-Vance
Genome-Wide Technique Aids Finding of New Alzheimer's Gene
Pericak-Vance says the discovery was made possible by a technique known as a
genome-wide association study (GWAS) that lets scientists look throughout the
entire genome for small differences, or variants, in long stretches of DNA that
are more common in people with a particular disease.
For the new study, the researchers used GWAS to look for gene variants in
about 1,100 people with late-onset Alzheimer’s disease and 1,000 people without
About 9% of those with late-onset Alzheimer's had the MTHFD1L variant on
chromosome 6, compared with only 5% of those who did not have Alzheimer's.
The researchers then replicated the findings in 2,500 people, about 1,300 of
whom had the disorder.
That replication gives "us more confidence" the finding is real, says Ron
Peterson, director of the Mayo Alzheimer's Disease Research Center in