Researchers from Salk Institute for Biological Studies, California, have identified a link between a risk gene — that increases the likelihood of Alzheimer’s disease — and plaques formed when protein pieces called beta-amyloid and tau tangles bundle together in the brain. This, according to the researchers, provides possible explanation as to how the presence of that extra gene causes the chronic neurodegenerative disease.

Nearly 7.5 million new cases of Alzheimer’s are diagnosed across the world annually and about 5 million Americans currently suffer from the disease.

Of all the risk genes identified so far in relation to Alzheimer’s, apolipoprotein E4 or ApoE4 gene has the strongest impact on the heightened chances of developing the disease. ApoE4 belongs to one of the three major versions of APOE gene. The other two variants are ApoE2 and ApoE3.

Some variants of the APOE are passed on to people from each parent. Those who get one copy of ApoE4 are at an increased risk of developing Alzheimer’s and those who receive two copies of the gene have an even higher risk, though not necessarily a certainty. Scientists estimate that ApoE4 is found in about 20 to 25 percent of Alzheimer’s cases.

Previous studies have suggested that ApoE4 may impact the way the brain removes beta-amyloid. “ApoE4 is the most predictive genetic change for late onset Alzheimer’s, but no one has really understood what's going on at the molecular level,” Alan Saghatelian, a Salk professor involved in the study, said in a statement.

Scientists had previously found that ApoE4 may degrade in a different manner compared to other versions of the APOE gene. But the protein that results in ApoE4’s breakdown was not known.

In a bid to find that protein, Saghatelian and research associate Qian Chu examined tissues for possible suspects and pinpointed on one enzyme called high-temperature requirement serine peptidase A1 (HtrA1). Researchers found that the enzyme HtrA1 was more active while accelerating the conversion of ApoE4 into smaller fragments, and less active while catalyzing the same reaction for ApoE3. This was found in both isolated proteins and human cells.

“There’s been an idea tossed around that ApoE4 breakdown products could be toxic,” Saghatelian said, adding, “Now, knowing the enzyme that breaks it down, we have a way to actually test this idea.”

The researchers also found that ApoE stops the enzyme from breaking down the tau protein, which is responsible for tau tangles linked to Alzheimer’s. This happens because the gene joins well to HtrA1.

“People have thought about tau or amyloid beta as things that cause Alzheimer’s, but this suggests that we need to think more globally about proteins that could be impacting tau or amyloid through biochemical pathways,” Saghatelian said.

However, the results need to be checked and corroborated in animal studies before researchers are sure that HtrA1 is the link between ApoE4 and Alzheimer’s in humans.

“But if they hold true, they could point toward a better understanding of the disease and potential new treatment strategies,” the researchers noted in the statement.