Alzheimer's Disease and other Dementias
Delaying Alzheimer’s by 10 Years
Medical research has yet to discover an Alzheimer’s treatment that effectively slows the disease’s progression, but neuroscientists at the University of California, Santa Barbara may have uncovered a mechanism by which onset can be delayed by as much as 10 years.
A release from the university notes that the mechanism is a gene variant — an allele — found in a part of the genome that controls inflammation. The variant appears to prevent levels of the protein eotaxin from increasing with age, which it usually does hand in hand with inflammation. The findings were published in September 2015 in the journal Molecular Psychiatry.
Lead author Matthew Lalli, who earned his Ph.D. working in UCSB’s Kosik Research Group, sequenced the genomes of more than 100 members of a Colombian family affected with early-onset Alzheimer’s. These individuals 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.
The release quotes co-author Kenneth S. Kosik, co-director of UCSB’s Neuroscience Research Institute and a professor in the Department of Molecular, Cellular and Developmental Biology, as saying, “We wanted to study those who got the disease later to see if they had a protective modifier gene. 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.”
Lalli used a statistical genetics approach to determine whether these outliers possess any protective gene variants, and he found a cluster of them. “We know that age is the greatest risk factor for Alzheimer’s beyond genetics,” said Lalli, who is now a postdoctoral fellow at Washington University in St. Louis. “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 UCSB researchers collaborated with UC San Francisco to study 150 individuals affected with Alzheimer’s or dementia. UCSF investigators 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 UCSF 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. “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,” Kosik explained.