A panel of 10 lipid metabolites can predict the development of either amnestic mild cognitive impairment (aMCI) or Alzheimer’s disease within two to three years with 90% sensitivity and 90% specificity, according to an article published online ahead of print March 9 in Nature Medicine.
“The defined 10-metabolite profile features PCs [phosphatidylcholines] and ACs [acylcarnitines], phospholipids that have essential structural and functional roles in the integrity and functionality of cell membranes,” said Mark Mapstone, PhD, Associate Professor of Neurology at the University of Rochester Medical Center in New York.
Of the 525 healthy, community-dwelling individuals ages 70 and older enrolled in the observational study, 74 met the criteria for aMCI or mild Alzheimer’s disease during the five-year follow-up. Of these participants, 46 had incidental findings at study entry, and 28 developed cognitive problems during a mean period of 2.1 years.
In the third year of the study, the investigators conducted untargeted metabolomic and lipidomic analysis on blood samples from 53 participants with either aMCI or Alzheimer’s disease, including 18 converters, and 53 cognitively normal controls. Blood samples from the converters were taken before and after conversion.
Analysis revealed that several amino acids and phospholipids were present in significantly different quantities between the two groups, and a further targeted analysis showed that the converter group had significantly lower plasma levels of serotonin, phenylalanine, proline, lysine, PC, taurine, and AC.
Dr. Mapstone and his colleagues identified a set of 10 metabolites that comprised PCs, lysophosphatidylcholine, and ACs, which were each found at much lower levels in the plasma of the converter group before conversion than in the plasma of the cognitively normal group. APOE e4 allele status did not significantly affect the classification of converters to aMCI or Alzheimer’s disease or the normal controls.
“These metabolites remained depleted after phenoconversion to aMCI or Alzheimer’s disease ... and were similar to the levels in the aMCI or Alzheimer’s disease group,” reported the researchers.
“We posit that this 10-phospholipid biomarker panel, consisting of PC and AC species, reveals the breakdown of neural cell membranes in those individuals destined to phenoconvert from cognitive intactness to aMCI or Alzheimer’s disease and may mark the transition between preclinical states where synaptic dysfunction and early neurodegeneration give rise to subtle cognitive changes,” said Dr. Mapstone.
—Bianca Nogrady