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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 (March 9th, 2014) in Nature Medicine, 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.
Howard J. Federoff, MD, PD, professor of neurology and executive vice president for health sciences at Georgetown University Medical Center, and his team of scientists found that a panel of 10 lipids—or fats—circulating in the blood could predict, with greater than 90 percent accuracy in the study population, which subjects 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. 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. “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”. 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 researchers are closing in on what Federoff calls a “network of molecules that defines an at-risk individual”. 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.”
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