Researchers have identified a panel of 10 lipid metabolites that can predict the development of either amnestic mild cognitive impairment or Alzheimer’s disease within 2-3 years with 90% sensitivity and 90% specificity.
"The defined ten-metabolite profile features PCs [phosphatidylcholines] and ACs [acylcarnitines], phospholipids that have essential structural and functional roles in the integrity and functionality of cell membranes," Dr. Mark Mapstone of the University of Rochester (N.Y.) and his colleagues wrote in Nature Medicine.
Of the 525 healthy, community-dwelling individuals aged 70 years and older enrolled in the observational study, 74 met the criteria for amnestic mild cognitive impairment (aMCI) or mild Alzheimer’s disease during the 5-year follow-up period – 46 who were incidental at entry to the study and 28 who converted over a mean time of 2.1 years (Nat. Med. 2014 March 9 [doi:10.1038/nm.3466]).
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 a number of amino acids and phospholipids that were significantly different between the two groups, and a further targeted analysis showed that the converter group had significantly lower plasma levels of serotonin, phenylalanine, proline, lysine, phosphatidylcholine, taurine, and acylcarnitine.
In particular, Dr. Mapstone and his associates identified a set of 10 metabolites that comprised phosphatidylcholines, lysophosphatidylcholine, and acylcarnitines, 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. Apolipoprotein E epsilon-4 allele status did not have a significant effect on the classification of converters to aMCI or AD or the normal controls.
"These metabolites remained depleted after phenoconversion to aMCI/AD ... and were similar to the levels in the aMCI/AD group," the researchers reported.
Dr. Richard J. Caselli
"We posit that this ten–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 AD and may mark the transition between preclinical states where synaptic dysfunction and early neurodegeneration give rise to subtle cognitive changes," Dr. Mapstone and his coworkers wrote.
Commenting on the study, Dr. Richard J. Caselli, professor of neurology at the Mayo Clinic in Scottsdale, Ariz., and clinical core director of the Arizona Alzheimer’s Disease Center, said that lipidomic studies represent a different approach from the usual proteomic and genomic approaches, although it was not possible to say whether any one approach would be more valid than another.
Dr. Caselli, however, said that a test using blood samples would have its advantages.
"Blood tests are always easier and often cheaper than spinal taps or PET scans (or any other brain imaging procedure) [and] they can also be repeated more easily to track disease progression," Dr. Caselli said.
"For patients with overt symptoms, even at the MCI stage, PET scans are quite sensitive. The problem is they are expensive and not always covered by insurance, so a less expensive and equally reliable blood test would certainly be welcome," he added.
The investigators and Dr. Caselli had no conflicts of interest to declare.