Researchers have discovered and validated a blood test that can predict with greater than 90% accuracy whether a healthy person will develop mild cognitive impairment or Alzheimers disease within three years.
Published March 9 on the website of the journal Nature Medicine, the study heralds the potential for developing treatment strategies for Alzheimers at an earlier stage, when therapy would be more effective at slowing or preventing onset of symptoms. It is described as the first known published report of blood-based biomarkers for preclinical Alzheimers.
The test identifies 10 lipids in the blood that predict disease onset. It could be ready for use in clinical studies in as few as two years and, researchers said, other diagnostic uses are possible.
Our novel blood test offers the potential to identify people at risk for progressive cognitive decline and can change how patients, their families and treating physicians plan for and manage the disorder, Howard J. Federoff, MD, PhD, the studys corresponding author and a professor of neurology and executive vice president for health sciences at Georgetown University Medical Center in Washington, D.C., said in a news release.
There is no cure or effective treatment for Alzheimers. Worldwide, about 35.6 million individuals have the disease and, according to the World Health Organization, the number will double every 20 years to 115.4 million people with Alzheimers by 2050.
Efforts to develop drugs that would slow or reverse the progression of Alzheimers disease have failed, Federoff noted, possibly because the drugs were evaluated too late in the disease process.
The preclinical state of the disease offers a window of opportunity for timely disease-modifying intervention, Federoff said. Biomarkers such as ours that define this asymptomatic period are critical for successful development and application of these therapeutics.
The study included 525 healthy participants ages 70 and older who gave blood samples upon enrolling and at various points in the study. Over the course of the five-year study, 74 participants met the criteria for either mild Alzheimers disease or amnestic mild cognitive impairment, in which memory loss is prominent. Of these, 46 were diagnosed upon enrollment and 28 developed aMCI or mild AD during the study (the latter group were categorized as converters).
In the studys third year, the researchers selected 53 participants who developed aMCI/AD, including 18 converters, and 53 cognitively normal matched controls for the lipid biomarker discovery phase of the study. The lipids were not targeted before the start of the study, but instead were an outcome of the study.
A panel of 10 lipids was discovered, which the researchers said appears to reveal the breakdown of neural cell membranes in participants who develop symptoms of cognitive impairment or AD. The panel was subsequently validated using the remaining 21 aMCI/AD participants (including 10 converters) and 20 controls. Blinded data were analyzed to determine whether the subjects could be characterized into the correct diagnostic categories based solely on the 10 lipids identified in the discovery phase.
The lipid panel was able to distinguish with 90% accuracy these two distinct groups: cognitively normal participants who would progress to MCI or AD within two to three years and those who would remain normal in the near future, Federoff said.
The researchers examined whether the presence of the APOE4 gene, a known risk factor for developing AD, would contribute to accurate classification of the groups but found it was not a significant predictive factor in the study.
We consider our results a major step toward the commercialization of a preclinical disease biomarker test that could be useful for large-scale screening to identify at-risk individuals, Federoff said. Were designing a clinical trial where well use this panel to identify people at high risk for Alzheimers to test a therapeutic agent that might delay or prevent the emergence of the disease.
Study access (via subscription or purchase): www.nature.com/nm/journal/vaop/ncurrent/full/nm.3466.html