A new $10.7 million, five-year project led by the University of Pittsburgh Graduate School of Public Health and Washington University School of Medicine in St. Louis will be the first comprehensive study of the genetic underpinnings of Alzheimer’s disease using whole genome sequencing.

With funding from the National Institute on Aging, the research team plans to identify the genetic variants, genes and pathways that lead to formation of plaques and tangles, two specific biomarkers that begin accumulating in the brains of people with Alzheimer’s 15 to 25 years before they show symptoms. 

Ilyas Kamboh, professor of human genetics and epidemiology at Pitt Public Health, and Carlos Cruchaga, professor of psychiatry at Washington University, are co-principal investigators on the project. Together, they intend to work on as many as 5,000 participants derived from the Pitt and Knight Alzheimer’s Disease Research Centers with a high risk of Alzheimer’s and the associated biomarker data to identify genetic variants that manifest decades before clinical symptoms of the disease.

“All of the clinical trials to find a drug to stop Alzheimer’s disease have failed because they’ve focused on patients who have already developed the disease, so they already had high levels of plaques and tangles,” Kamboh said. “Once you have the plaques and tangles, it seems to be an irreversible process, so we’re focused on the preclinical stage of the disease.”