The Kosik Group at the University of California, Santa Barbara’s Neuroscience Research Institute have discovered a mutation that can slow the onset of Alzheimer’s disease by ten years.
Alzheimer’s disease is the most common form of dementia, affecting over 5 million people across America. It is one of the top 10 causes of death in America, and the only disease in the list of top 10 without prevention techniques, treatment, or a cure.
The research was conducted on an extended Colombian family of 4,000 members with a rare genetic mutation that leads to complete Alzheimer’s by age 49.
“Every biological trait is produced by a combination of genetics and environment,” said Matthew Lalli, a graduate student of the Kosik Group. “By studying a population with a definitive cause of Alzheimer’s disease, which shares a very similar environment (lifestyle, diet, education, location, etc), our hypothesis was that we would be able to find the genetic contributors affecting age of onset of Alzheimer’s in this population.”
Lalli sequenced the genome of 117 members, identifying a combination of alleles on Chromosome 17 that is associated with a delayed onset of the disease.
“We wanted to study those who got the disease later to see if they had a protective modifier gene,” said co-author and professor Dr. Kenneth S. Kosik. “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 a gene variant actually pushes the disease onset as much as 10 years later.”
Through statistical genetic analysis, Lalli found the gene variant: a consistent level of eotaxin with increasing age. “We know that age is the greatest risk factor for Alzheimer’s beyond genetics,” said Lalli. “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.”
“Although the gene mutation in the Colombian population is extremely rare, this variant is not,” Kosik said. “It occurs in about 30 percent of the population, which means it has the potential to protect a lot of people against Alzheimer’s.”
To better understand the impact of this gene variant, further experiments need to be conducted. “An immediate future step for this finding, and all genetic findings, is to confirm the results in an independent population,” said Lalli. “Identifying the cell types that secrete eotaxin in both healthy and diseased conditions is another top priority to better understand the role of eotaxin in Alzheimer’s.”
“If confirmed, these results would pinpoint a novel molecule modifying the course of Alzheimer’s disease, providing a target for future therapies,” Lalli added. “This means that a clinical trial to see if these drugs can treat Alzheimer’s could happen in the near future… Our results add to the growing body of evidence that inflammation contributes to Alzheimer’s disease, which should help draw more attention and funding to this field.”