Harvard researchers announced a breakthrough in efforts to understand the genetic basis of late-onset Alzheimer’s disease earlier this month.

The team—led by scientists at the Harvard-affiliated Mass. General Hospital—identified four new genes linked to the degenerative neural disease. Only one other gene had been previously associated with the illness.

The findings, published in the Nov. 7 issue of the American Journal of Human Genetics, came from an analysis of more than 400 families with three family members suffering from the debilitating disorder, which afflicts 2.4 to 4.5 million Americans.

The findings could facilitate more accurate predictions of Alzheimer’s and provide “new biological pathways” towards therapies for the disease, according to Harvard Medical School Professor Rudolph E. Tanzi, who led the effort.

The study drew on data from the hospital’s MassGen Institute for Neurological Disease, which has been collecting family genetic data since 1989 to enable such an analysis.

The screen of over 500,000 gene markers turned up five genes with strong associations with the onset of Alzheimer’s. Only one of those, the protein APOE, had been associated with the disease before.

The breadth of the genetic screen—the largest conducted for Alzheimer’s today—enabled the scientists to discover genes that otherwise may never have been tied to the disease, according to Tanzi.

“You get genes you would never have dreamed of,” Tanzi said. “That’s the way genetics should be done. You should be surprised.”

The gene discovered on chromosome 14, which had the strongest association of the five, was also the only one identified that had not been observed before in any context, Tanzi said. “That’s always the most fun,” he added.

The study broke new ground in part because technology developed in the past three or four years enabled the team to probe over a billion individual genetic markers with far greater speed than previously possible, Tanzi said.

Alzheimer’s is a fatal degenerative disease that can lead to a variety of dementia symptoms, including confusion, irritability, memory loss, and the eventual failure of bodily functions.

Tanzi said his team will continue their family-based research, focusing on the newly identified genes, with the “long-term vision” of creating new therapies to control the progression of Alzheimer’s.

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