New Genes May Contribute to Alzheimer’s.

Alzheimer’s disease is the most common cause of dementia, and the fifth leading cause of death in those 65-years and older in the US. Despite the growing prevalence of Alzheimer’s, the genetic and environmental factors that make some more susceptible to the development of the disease is still not well understood.

Now, researchers from the School of Public Health and the School of Medicine, working with scientists across the nation on the Alzheimer’s Disease Sequencing Project, have discovered new genes that will further the current understanding of the genetic risk factors that predispose people to the development of Alzheimer’s.

The study, published in Molecular Psychiatry, identifies three new genes that had not previously been linked to Alzheimer’s, as well as several new variants in genes that had been associated with the disease.

“Many of our findings will provide insight into disease mechanisms and targets for biological experiments to gain further understanding about the role of these genes in Alzheimer’s disease pathogenesis,” says corresponding author Lindsay A. Farrer, professor of epidemiology and biostatistics, and chief of biomedical genetics and professor of medicine, neurology, and ophthalmology at MED.

By comparing the exomes (gene-coding portions of entire genetic sequences) of nearly 6,000 individuals with Alzheimer’s, and 5,000 cognitively healthy older adults, the researchers were able to find rare variations in genes that they believe may contribute to the development of common Alzheimer’s disease.

The newly discovered genes may suggest an inflammatory response and changes in the protein production. These combined changes are thought to contribute to the overall neurodegeneration witnessed in older adults with the disease.

The authors wrote that further research will need to be done to find other genes hidden throughout the genome, as the current paradigm is that many genes contribute to the development of Alzheimer’s. They also wrote that they hope their work will help bridge the knowledge gaps of the genetic architecture related to Alzheimer’s, which is a necessary step toward a better understanding of mechanisms leading to the disease and eventual therapeutic treatments.

The Alzheimer’s Disease Sequencing Project was developed by the National Institutes of Health (NIH) in response to the National Alzheimer’s Project Act milestones to fight Alzheimer’s.

“This large and deep gene sequencing study is an important part of identifying which variations may play a part in risk of getting Alzheimer’s or protection against it,” says Eliezer Masliah, director of the Division of Neuroscience at the National Institute on Aging, part of NIH. “Big data efforts like the ADSP are really helping research move forward. Identifying rare variants could enhance our ability to find novel therapeutic targets and advance precision medicine approaches for Alzheimer’s disease.”

The other SPH co-authors of the study were: alumnus Yuning Chen (GRS/SPH’18); L. Adrienne Cupples, professor of biostatistics; postdoctoral associate Chloe Sarnowski; Xiaoling Zhang, assistant professor of biostatistics; Kathryn L. Lunetta, professor of biostatistics; Anita L. DeStefano, professor of biostatistics; and Josée Dupuis, professor and chair of biostatistics.