Researchers Discover Mutated Protein Linked to Increased Risk of Alzheimer’s Disease

A caregiver comforts a patient suffering from Alzheimer's disease. AP Photo/Apichart Weerawong

A new mutated protein has been discovered that is connected to a significant increase in the risk of an individual developing Alzheimer’s disease, according to a study by the University of Southern California (USC).

“The protein, called SHMOOSE, is a tiny ‘microprotein’ encoded by a newly discovered gene within the cell’s energy-producing mitochondria. A mutation within this gene partially inactivates the SHMOOSE microprotein and is associated with a 20-50 percent higher risk for Alzheimer’s disease across four different cohorts. Nearly a quarter of people of European ancestry have the mutated version of the protein,” a Sept. 20 press release states.

The substantial risk and high prevalence of the mutation differentiates SHMOOSE from other proteins involved in the disease. The limited number of other gene mutations that have been identified as risk factors for Alzheimer’s increase the risk of Alzheimer’s by less than 10 percent compared to SHMOOSE’s 20 to 50 percent.

Brendan Miller, an author of the study, used big data to identify the SHMOOSE microprotein. According to researchers, SHMOOSE is the first mitochondrial-DNA-encoded microprotein to have been detected using mass spectrometry as well as antibodies.

Pinchas Cohen, professor of gerontology and senior author of the study, believes the discovery paves the way for developing precision medicine-based therapies for the disease.

“Administration of SHMOOSE analogs in individuals who carry the mutation and produce the mutant protein may prove to have benefit in neurodegenerative and other diseases of aging,” he said, according to the release.

Alzheimer’s in America, FDA Medicine Approval

In the United States, over 6 million people are estimated to be living with Alzheimer’s, a number that’s expected to more than double and rise to about 13 million by 2050 according to the Alzheimer’s Association.

The COVID-19 pandemic has had a negative effect on people suffering from Alzheimer’s and other forms of dementia as death rates rose by 16 percent during this period.

Alzheimer’s is one of the top 10 leading causes of death in the United States, the fifth leading cause of death among adults aged 65 and above, and the sixth leading cause of death among adults overall, according to data from the U.S. Centers for Disease Control and Prevention.

In June 2021, the U.S. Food and Drug Administration (FDA) approved an Alzheimer’s drug called aducanumab, which is marketed under the brand name Aduhelm. This was the first Alzheimer’s medication approved by the agency since 2003.

However, the FDA decision was steeped in controversy as the agency granted accelerated approval for Aduhlem in June. Within a week of the approval, three members from an FDA advisory committee resigned.

Dr. Aaron Kesselheim, who was among those who resigned, called the FDA decision “probably the worst drug approval decision in recent U.S. history” in his resignation letter.

In a tweet posted June 7, 2021, he wrote: “Accelerated Approval is not supposed to be the backup that you use when your clinical trial data are not good enough for regular approval.”

The other two who resigned, neurologists David Knopman and Joel Perlmutter, wrote in an article for Neurology that there were real risks associated with the side effects of the drug and no statistically significant benefits.