Novel Biomarker Panel May Predict Who Will Develop Cognitive Impairment, Including Alzheimer’s Disease

VBCN - April 2014 Volume 1, No 1

A newly released study has found a set of 10 lipids from peripheral blood that can predict a neurodegenerative process that may be linked to Alzheimer’s disease (AD) or other types of cognitive impairment using a blood test to identify these biomarkers (Mapstone M, et al. Nat Med. 2014;20:415-418). This led the media around the globe to declare this a potential game-changing breakthrough in early detection of the disease.

Closer examination, however, indicates that this is only one step in the long process of creating an accurate blood test for predicting the development of cognitive impairment.

The study was conducted by lead author Mark E. Mapstone, PhD, MA, Associate Professor of Neurology, University of Rochester Medical Center, NY, and colleagues from Georgetown University, Washington, DC.

“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 aMCI [amnestic mild cognitive impairment] 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 colleagues wrote.

The team sifted through plasma samples of 451 people aged ≥70 years who were cognitively normal, and 74 who had aMCI or AD. The objective of the study was to find an amino-acid and phospholipid profile that is unique to people who will go on to develop aMCI or AD.

Dr Mapstone and colleagues iden­tified a set of 8 phosphatidylcholine molecules and 2 acylcarnitines that were less abundant in the plasma of people who had transitioned over a 2- to 3-year span from being cognitively normal to the aMCI state or to AD than in the blood of those who remained cognitively normal.

The 10-metabolic lipids panel had a sensitivity and specificity of 90% for being able to discriminate between individuals who switched from being cognitively normal to having cognitive impairment and those who remained cognitively normal.

“The more immediate questions we have related to this work are, ‘Can this blood test be used to screen a larger and more diverse population?’ and ‘Can it be used to screen younger people to predict onset of disease?’” Dr Mapstone told Value-­Based Care in Neurology.

Study Details
A total of 525 community-dwelling individuals aged ≥70 years were enrolled in the study; of these, 46 had aMCI or mild AD at baseline, and another 28 developed one of these conditions in an average of 2.1 years.

In the third year of the 5-year study, the investigators selected 53 participants with aMCI or mild AD, including 18 patients who had developed one of the conditions during the study, for serum analysis for possible metabolomic and lipidomic biomarkers; the investigators also selected 53 matched cognitively normal participants to act as controls. In addition, the researchers created an internal cross-validation subset that included the remaining 10 patients who had developed aMCI or mild AD during the study, and 11 of the participants who had aMCI or AD at baseline, together with 20 matched controls.

The initial search for biomarkers yielded a set of 10 metabolites that comprised 8 phosphatidylcholine molecules and 2 acylcarnitines; a targeted biomarker analysis in a separate group of 40 participants that served as an independent, blinded, cross-validation, revealed similar levels of the 10 biomarkers to the initial search.

Statistical analyses showed that the 10-metabolite panel had a 90% sensitivity and a 90% specificity in classifying which individuals would develop aMCI or mild AD, and which individuals would not. The investigators repeated the analyses with the addition of apolipoprotein E to the metabolite panel—because apolipoprotein E is implicated in the development of AD—and found that this did not increase the accuracy of the test.

The authors cautioned that the panel needs to be validated by other researchers before it can be refined and put into clinical use.

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