A Brigham Young University researcher has helped identify two genes associated with Alzheimer's disease, a finding that one day could help identify and provide early intervention for those most at risk of developing the disease.
John "Keoni" Kauwe, assistant professor of biology, has been part of an international research team that has been examining genetic risk factors for Alzheimer's disease for the past several years. The team's most recent findings linking the existence of two genes with the disease was reported in the journal Nature Genetics earlier this month.
The research team looked at hundreds of thousands of bits of DNA collected from nearly 4,000 Alzheimer's patients and compared it with the genetic code of about 7,000 healthy people. Genetic variations were noted more commonly in the sick patients than the healthy ones, leading to the discovery of the two genetic variants.
Led by researchers from Wales, the team identified single "letter" differences — called single nucleotide polymorphisms, or SNPs — in the DNA which surrounds the gene for clusterin, known as CLU or APOJ. Clusterin is believed to help rid the brain of a plaque-forming molecule that kills neurons in the brain.
The team also discovered variants close to a gene encoding the PICALM protein, which helps control what gets into individuals cells, possibly including the harmful, plaque-forming molecules known as amyloid-beta.
Kauwe said the developments are important in creating a foundation for further research into the specific causes of Alzheimer's, noting that clinical trials are now under way on people who have a defined genetic risk for developing the disease. Researchers are trying to prolong their healthy status by using drugs and lifestyle interventions. The new discoveries "provide us with a tool to recommend those preventative activities," for patients participating in the trials, he said.
"We can justify treatment (with experimental drugs) for someone if we know they have a greatly increased risk for the disease," based on genetic makeup. "Without an understanding of their risk (to develop Alzheimer's) we can't justify treating them with drugs that may have side effects," Kauwe said.
Kauwe said Alzheimer's research has long been hampered by the difficulty of collecting large groups of people with the disease to study with a corresponding "control group" of the same age who don't have Alzheimer's or dementia.
"It's different than looking at something like heart disease where you can study younger people and the data is easier to collect."
Until recently, most Alzheimer's studies were conducted at individual research centers, meaning their study groups were small and couldn't easily be compared with larger populations.
The study Kauwe has been working on, as well as another also reported in the same Nature Genetics article, "are the first that have pulled research together from multiple centers and done the work together. We really just needed thousands and thousands of people in the studies to see the genetic effects."
Though the research doesn't provide enough information about who will develop the disease, Kauwe said it does allow researchers to say whether someone has a slightly higher probability of developing Alzheimer's.
Now scientists can look "at every single genetic variant in the region where we see these associated variants and try to understand which of those directly affect function or protein or levels of protein," he said.
"Once we find that, we'll have much more confidence in how the variant is affecting disease and using it as a predictive factor."