This Gene Variant Delays Alzheimer’s By 10 Years

When researchers sequenced the genomes of more than 100 members of a Colombian family affected with early-onset Alzheimer’s, they discovered a mechanism that seems to delay the disease.

The family members have a rare gene mutation that leads to full-blown disease around age 49. However, in a few outliers, the disease manifests up to a decade later.

“We wanted to study those who got the disease later to see if they had a protective modifier gene,” says Kenneth S. Kosik, a biology professor at the University of California, Santa Barbara. “We know they have the mutation. Why are they getting it so much later when the mutation so powerfully determines the early age at onset in most of the family members?

“We hypothesized the existence of gene variant actually pushes the disease onset as much as 10 years later.”

Age and Alzheimer’s

Matthew Lalli, who earned his PhD at UC Santa Barbara and is the study’s lead author, used a statistical genetics approach to determine whether these outliers possess any protective gene variants. He found a cluster of them.

Lalli, who is now a postdoctoral fellow at Washington University in St. Louis, says:

“We know that age is the greatest risk factor for Alzheimer’s beyond genetics. The variant that we found is age-related, so it might explain the actual mechanism of how an increase in age increases the risk of Alzheimer’s—through a rise in eotaxin.”

To replicate the findings, the UC Santa Barbara researchers collaborated with UC San Francisco to study 150 individuals affected with Alzheimer’s or dementia. They measured levels of eotaxin in the participants’ blood and collected DNA samples to confirm who carried the gene variant identified in the Colombian population.

The results showed that people in the UC San Francisco study with the same variant had eotaxin levels that did not rise with age. They also experienced a modest but definite delay in the onset of Alzheimer’s.

30% of the Population

“If you have that variant, maybe one way to delay or reduce your risk for Alzheimer’s is by genetically holding in check the normal increase in eotaxin that occurs in most of the population,” says Kosik, a coauthor of the study

“Although the gene mutation in the Colombian population is extremely rare, this variant is not,” he adds. “It occurs in about 30 percent of the population, which means it has the potential to protect a lot of people against Alzheimer’s.”

Previous independent work at Stanford University has shown that adding eotaxin to young mice made them functionally older. Stanford is also currently testing whether blood transfusion from young individuals to older ones confers benefits.

“The results of this work may provide additional evidence that eotaxin plays a role in the deleterious effects of aging,” says Lalli.

Adds Kosik:

“We have an important preliminary finding. If this is a true mechanism of Alzheimer’s progression, then we can modify the level of eotaxin in individuals to treat the disease. But our results must be replicated and proved by other laboratories—and in larger populations.”

Top Photo:Ashley Adams/flickr

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