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Monday, April 7, 2014

Newly Identified Blood Biomarkers for Alzheimer's Disease
by Jamie Talan

Researchers identified 10 lipids or fats that were powerful enough to predict phenoconversion to either mild cognitive impairment (MCI) or Alzheimer’s disease (AD) within a two- to three-year study period with 90 percent accuracy.

     While the findings emerged from a relatively small sample of patients, experts in the field told Neurology Today that the results, published online first on March 9 in Nature Medicine, are encouraging and should be replicated in larger data sets. Identifying preclinical AD disease with a blood test — much like screening for cholesterol for heart disease and/or stroke — could change the course of the disease for future generations of older people, they said.

Howard J. Federoff, MD, PhD, executive dean of Georgetown University School of Medicine, who led the research team, noted that others have identified potential blood markers but none have been replicated so far. The problem, he said, is that there are substantial circadian variations in metabolism and finding a true signature is difficult.

      Knowing that there are changes in metabolism and gene expression throughout the day and in response to eating and medication, the researchers added a critical design change to their study: they collected blood after a night of fasting and before a person had any of his or her daily medications on board. He believes that this pure blood sample helped in the identification of these newly identified markers.

“I think that our success in identifying these markers is because of the way we looked at the blood and our collection method,” said Dr. Federoff.

The researchers enrolled and monitored 525 healthy people for five years; all were at least 70 years old and were living independently in the community. Over the course of the study, 74 of them met criteria for MCI or mild AD. Forty-six had incidental MCI or AD when they entered the study and 28 had phenoconverted from a cognitively fit state to MCI or AD. The average time to phenoconversion was 2.5 years. The scientists had a control group of age-, gender-, and education-matched cognitively normal people.  
     Using tandem mass spectrometry to identify metabolites, the researchers analyzed 124 plasma samples from 106 study participants. They were able to identify and qualify lipids, amino acids, and biogenic amines. 

In the third year of the study, they selected 53 people diagnosed with MCI or AD whose blood would be screened for metabolomics and lipidomic biomarker discovery. Eighteen patients had converted during the observational period. They compared the findings with 53 people in the control group. 

Dr. Federoff said that the analysis showed significantly lower plasma levels of serotonin, phenylalanine, proline, lysine, phosphatidylcholines (PC), taurine, and acylcarnitines (AC) in the converters. They identified 10 lipids that were depleted in the converters and not the controls.

“We posit that this ten-phospholipid biomarker panel…reveals the breakdown of neural cell membranes in those individuals destined to phenoconvert from cognitive intactness to amnesic MCI or AD, and may mark the transition between preclinical states where synaptic dysfunction and early neurodegeneration give rise to subtle cognitive changes,” the scientists wrote in the Nature Medicine paper.
“Our data has led to a new set of biological insights,” Dr. Federoff added. “This is an area of biology we have to probe more deeply.”
    Stay tuned for the full discussion of the findings and their implications for Alzheimer's researchers and patients in the April 17 issue of Neurology Today. For now, read our collection of articles on the search for Alzheimer's disease biomarkers: