Researchers Discover 6 Gene Mutations that Increase Alzheimer’s Risk

It’s not well understood exactly how much of Alzheimer’s disease is genetic and how much is based on lifestyle choices, but researchers are getting closer to knowing the truth. Recently, they’ve discovered six gene mutations that appear to significantly affect a person’s chances of developing the disease.

For this study, called “Analysis of high-risk pedigrees identifies 12 candidate variants for Alzheimer’s disease” and published in the journal Alzheimer’s & Dementia, researchers analyzed the genes of 19 Utahan families where Alzheimer’s occurred in higher-than-average numbers.

The team examined all protein-coding genes in the families using a genetic test and identified genes shared between cousin pairs in each family. “We then used a series of filtering criteria to identify rare genetic variants that were most likely contributing to the excess Alzheimer’s disease in each family,” says Justin Miller, Ph.D., assistant professor at the University of Kentucky College of Medicine and the study’s co-first author.

If at least one set of cousins shared a gene mutation, the researchers compared this mutation to large publicly available datasets. If they met four specific criteria, they were tagged as risk factor candidates for Alzheimer’s disease.

The team found 12 genes that impacted Alzheimer’s disease risk, and six of them were newly discovered genes that may contribute to the increased risk of Alzheimer’s: PELI3, FCHO1, SNAP91, COX6A2, MUC16, and PIDD1.

These gene mutations are actually fairly common, but there are a few rare ones that may impact Alzheimer’s prevalence among families too, including ABCA7, TTR, and NOTCH3. These mutations have all been previously recognized for their Alzheimer’s risk, but they’re not as commonplace as the six newly identified gene mutations.

According to researchers, “the presence of rare variants identified here may explain the prevalence of [Alzheimer’s disease] mortality in 19 of the 36 [Alzheimer’s]-affected individuals” from these high-risk families.

Of course, these six genes are far from being the only Alzheimer’s-related genes ever identified. There are now more than 30 gene variants associated with the disease. However, the research team estimates that still “more than 40% of the genetic variance of [Alzheimer’s disease] remains uncharacterized.”

“Identifying people with increased risk for Alzheimer’s disease before they become symptomatic may lead to earlier and more effective interventions,” says Miller.

The researchers hope their findings can help with the further development of new targets and therapeutic approaches for Alzheimer’s disease. They believe that their approach in identifying rarer mutations in families with high disease occurrence is a “powerful and efficient method” for finding new genes behind the disease, “particularly when coupled with external datasets that contain meaningful data about disease risk.”

Like all studies, of course, this one has its limitations. The small sample size, absence of non-white ethnicities, and the fact that only death certificate data was used to identify Alzheimer’s diagnoses may mean that more research is needed to corroborate the data. But researchers still hope that their work is a strong step forward toward understanding the genetic processes behind Alzheimer’s disease.