Gene variant linked to a 10-year delay in Alzheimer's onset

By studying a group of outliers in a Colombian family known for the prevalence of early-onset Alzheimer's, investigators at UC Santa Barbara believe they may have fingered a new drug target that could delay the disease by a decade or more.

Building on earlier work that linked higher levels of the protein eotaxin with accelerated aging, the team concluded that a genetic variant found among the outliers had helped rein in levels of the protein. And that function helped slow the advance of Alzheimer's.

UCSB's Kenneth Kosik

"We wanted to study those who got the disease later to see if they had a protective modifier gene," said co-author Kenneth Kosik, co-director of UCSB's Neuroscience Research Institute and a professor in the Department of Molecular, Cellular and Developmental Biology. "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."

Then they studied a separate population of Alzheimer's patients at UC San Francisco, concluding that the same genetic variant appeared to be responsible for a "modest" but clear delay in disease onset among a group of those patients. The results were published in the journal Molecular Psychiatry.

Adding to the significance of the work, this particular genetic variant occurs in 30% of the population, which would make it a prime target for a large segment of the population. But there's a lot of work left to do before the investigators can start advancing a new therapeutic program.

"We have an important preliminary finding," said Kosik. "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."

Alzheimer's R&D over the past decade has proven to be one of the most frustrating fields in the industry, with an extraordinarily high failure rate. This is one disease where triggers and treatments have a long way to go in blunting a disease that affects millions of people around the globe.

- here's the release
- read the research article

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