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Blood Test Identifies Those at Risk for Cognitive Decline, Alzheimer’s Within 3 Years

Preclinical biomarker assay may be on the horizon

Researchers at Georgetown University 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 Alzheimer’s disease (AD) within 3 years.

Described in the April issue of Nature Medicine, the study heralds the potential for developing treatment strategies for AD at an earlier stage, when therapy would be more effective at slowing or preventing the onset of symptoms. It is the first known published report of blood-based biomarkers for preclinical AD.

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 2 years, and other diagnostic uses are possible, the researchers say.

There is no cure or effective treatment for AD. Worldwide, about 35.6 million individuals have the disease and, according to the World Health Organization, that number will double every 20 years to 115.4 million people with AD by 2050.

According to corresponding author Howard J. Federoff, MD, PhD, there have been many efforts to develop drugs to slow or reverse the progression of AD, but all of them have failed. He said one reason may be that 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 new study included 525 healthy participants aged 70 years and older who gave blood samples upon enrolling and at various time points during the study. Over the course of the 5-year investigation, 74 participants met the criteria for either mild AD or amnestic mild cognitive impairment (aMCI), in which memory loss is prominent. Of these participants, 46 were diagnosed upon enrollment, and 28 developed aMCI or mild AD during the study. The latter subjects were called “converters.”

In the study’s third year, the researchers selected 53 participants who had 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 were an outcome of the study.

A panel of 10 lipids was discovered. According to the researchers, this panel 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 2 to 3 years, and those who would remain normal in the near future,” Federoff said.

The researchers also examined whether the presence of the APOE4 gene, a known risk factor for developing AD, would contribute to accurate classification of the study groups. They found the gene was not a significant predictive factor in this 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. “We’re designing a clinical trial where we’ll use this panel to identify people at high risk for Alzheimer’s to test a therapeutic agent that might delay or prevent the emergence of the disease.”

Source: Georgetown University Medical Center; March 9, 2014.

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