Despite decades of research and investment, the genetic underpinnings of Alzheimer’s disease are still largely unknown, stymieing efforts at drug development and early diagnosis. To change that, a new grant will support the first comprehensive study to use whole genome sequencing to address critical gaps in knowledge about the disease. The $10.7 million, five-year project is led by researchers at Washington University School of Medicine in St. Louis and the University of Pittsburgh Graduate School of Public Health.
Funded by the National Institute on Aging of the National Institutes of Health (NIH), the research team plans to identify the genetic variants, genes and pathways that lead to formation of plaques and tangles, two specific signs of disease — called biomarkers — that begin appearing in the brains of people with Alzheimer’s 15 to 25 years before they show symptoms.
“Genetic studies of measurable traits such as plaques and tangles provide advantages over other classic case-control studies, because these traits appear earlier and are more closely related to the biology behind the disease,” said Carlos Cruchaga, a co-principal investigator of the study and the Reuben Morriss III Professor of Neurology at Washington University School of Medicine. “In addition, studying these traits is more likely to lead to the identification of druggable targets along the genetic pathways that lead to disease. This genetic information can help us better predict disease risk at the individual patient level.”
Cruchaga, also a professor of psychiatry, is working with co-principal investigator Ilyas Kamboh, professor of human genetics and epidemiology at Pitt Public Health. Together, they plan to study as many as 5,000 participants at high risk for Alzheimer’s. The researchers will gather biomarker data to identify genetic variants that appear decades before clinical symptoms of the disease.