New Blood Test Predicts Risk of Alzheimer’s, Mild Dementia

MARCH 9, 2014—For the first time in decades of research aimed at cracking Alzheimer’s disease, a team led by Georgetown University Medical Center investigators has developed and validated a simple blood test that can predict which individuals will experience cognitive decline or Alzheimer’s disease in two or three years.

The finding, published online today in Nature Medicine and to be featured in the April print issue, offers new hope for the development of drugs to delay or possibly prevent onset of the disease, for which there is currently no treatment. The numbers of people with Alzheimer’s are expected to explode – from 35.6 million worldwide today to an estimated 115.4 million by 2050.

“This is a very exciting finding because it finally gives us a good opportunity to make clinically meaningful advances in Alzheimer’s disease research and treatment,” says the study’s senior investigator, Howard J. Federoff, MD, PD, professor of neurology and executive vice president for health sciences at Georgetown University Medical Center.

The Georgetown team also included Amrita K. Cheema, PhD, Massimo S. Fiandaca, MD, Xiaogang Zhong, PhD, Timothy R. Mhyre, PhD, Linda H. MacArthur, PhD, and Ming T. Tan, PhD.

Getting Ahead of Symptoms

Federoff led a team of scientists that found a panel of 10 lipids—or fats—circulating in the blood could predict, with greater than 90 percent accuracy in the study population, who would experience symptoms of cognitive decline or Alzheimer’s disease within three years.  

The five-year study followed 525 individuals in California and New York who were 70 years of age or older. Of the group, 46 were diagnosed with mild cognitive impairment or mild Alzheimer’s disease at the time they enrolled, and 28 went from having normal cognitive function to an impaired memory status during the study period. The blood test revealed marked differences in lipids between those who developed cognitive impairment or Alzheimer’s, and those who developed no signs of disease.

Investigators chose this age group because they were the most likely to develop memory problems within five years.

In addition to several Georgetown investigators, other team members include researchers from the University of Rochester, the University of California-Irvine, Rochester General Hospital, Unity Health System in Rochester, Temple University School of Medicine and Regis University School of Pharmacy in Denver.

The team determined that the 10 predictive lipids were molecules emanating from the destruction of brain cells.

The knowledge that a cognitively normal participant in a clinical trial possesses this telltale lipid profile will allow drug developers to see if experimental agents can prevent the onset of memory impairment at an earlier stage, Federoff says.

“There have been many efforts to develop drugs that were thought to modify the history of Alzheimer’s disease and sadly, all of them have failed. One of the reasons for this is that the agents were tested in patients who already have the disease and that is the wrong stage to evaluate disease-modifying therapies,” Federoff says.

While it is premature to know if treatment for a few years before the onset dementia can make a difference, Federoff notes that “for the first time, the potential for drug therapy can be tested in a smart and rigorous way.”

‘The Story is Getting a Lot Tighter’

This is the first in what is expected to be a series of studies that will compare the molecular state in the brains of individuals with and without early signs of dementia.

The research team is conducting a systems biology analysis of everything from the plasma lipids — a straightforward quantitative test — to genomic, transcriptomic and proteomic profiles.

They have sequenced the genome of every one of the participants included in this study, collecting 12 terabytes of data—or 12 trillion digital bytes of information. The researchers are closing in on what Federoff calls a “network of molecules that defines an at-risk individual.”

“The story is getting a lot tighter and the Nature Medicine report is just the very first volley. My anticipation is that eventually we are going to be able to link all of those informational molecules into a coherent story that might even begin to address what is the underlying mechanism that puts people at risk,” Federoff says.

One key finding is that the presence of the APOE4 gene, a known risk factor for developing Alzheimer’s, did not augment the diagnostic accuracy of the test.  This is important because it suggests that “in at-risk individuals, APOE is playing an insignificant small role” and that this new lipid test is “much more predictive.”

Information is Power

As the researchers continue to refine their analysis, they are looking to test the efficacy of the lipid profile in more diverse populations.

“When perfected, this very simple and inexpensive test can be conducted using the technology that exists in almost every clinical lab in the world,” Federoff says.  

“Knowing you are at risk for cognitive impairment can be valuable for planning, but it is most beneficial if you can modify your risk — and that is what we all seek and now have a helping hand in finding,” he says.

Federoff and Georgetown researchers Amrita K. Cheema and Massimo S. Fiandaca along with Mark Mapstone of the University of Rochester are named as co-inventors on a patent application filed by Georgetown and the University of Rochester related to the technology described. 

The National Institutes of Health (R01AG030753) and the Department of Defense (W81XWH-09-1-0107) funded the study.

For additional information on this study, view this video.

By Renee Twombly
GUMC Communications