The world’s largest Alzheimer’s study has made a gene discovery that could lead to treatments

Researchers have found two novel genes that increase anindividual’s risk of developing Alzheimer’s disease (AD). This disorder is the
leading cause of dementia and has an estimated heritability —genetic factor
causing variation in the population, or an inherited trait— of 70%.

Details from the study

The research team worked with Cardiff University’s Dementia
Research Institute in the U.K. to reveal the new genes associated with the brain
disorder that affects thinking and behavior, often starting with memory loss.

The study was published on Nov. 21 in the journal Nature Genetics.

Researchers from across the globe compared data that
involved 32,558 genetic codes from both patients who had Alzheimer’s disease,
and healthy participants. For the study, 16,036 individuals had Alzheimer’s
disease and 16,522 individuals did not have AD.

New mutations found within genes that could cause Alzheimer’s

The study found various new genes and certain mutations
within those genes that can lead to the onset of developing Alzheimer’s
disease. The new genes contain mutations that are rare, but also detrimental.   These
mutations were found in the genes called ATP8B4 and ABCA1, both of which could
potentially lead to an increased risk of developing Alzheimer’s disease. They
also discovered a genetic alternation — gene abnormality — in the gene known as
ADAM10.

Researchers believe that the study allows them to assess
variance in the immune system and brain processing. “These findings point
us towards very specific processing in the brain, which includes differences in
the brain’s immune system and how the brain processes cholesterol. These
differences impact brain functioning and leads to the development of
Alzheimer’s disease,” said Julie Williams, a professor, director of the Dementia
Research Institute at Cardiff University, and a co-author on the study.

Exome sequencing data is used to identify variants of AD

In most assessments of AD, researchers used genome-wide
association studies (GWAS), which are observational tests that look at all of
the genetic information within DNA to find connections. However, GWAS does not catch
the risk from rare variants of mutations. The researchers for this study used
exome sequencing data to identify variants that cause Alzheimer’s disease. The statistics
from exome sequencing is smaller than GWAS and allows for researchers to
identify rare mutations.

Alzheimer’s disease currently has no cure. However, researchers
believe that new discoveries of gene mutations can get them closer to
discovering treatment options and preventative measures. Although older age is
a risk factor for developing AD, younger people are starting to get early onset
Alzheimer’s disease, which occurs in people between the ages of 30 to mid-60s. Genetic
factors play a large role in developing AD early.  

The future and knowing who is at risk for AD

The research allowed the team to understand who is most
likely to develop AD by assessing the new gene mutations that can potentially
increase the risk of developing this progressive disease. “This study helps
expand our knowledge about who is at risk of developing this form of dementia.
These genetic discoveries also allow us to understand the mechanisms underlying
Alzheimer’s, as well as create genetic models of the disease to develop
targeted therapies in the future—through new drug-based treatments or even gene
therapy,” Williams stated.