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Plasma phospholipids identify antecedent memory impairment in older adults

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Alzheimer's disease causes a progressive dementia that currently affects over 35 million individuals worldwide and is expected to affect 115 million by 2050 (ref. 1). There are no cures or disease-modifying therapies, and this may be due to our inability to detect the disease before it has progressed to produce evident memory loss and functional decline. Biomarkers of preclinical disease will be critical to the development of disease-modifying or even preventative therapies2. Unfortunately, current biomarkers for early disease, including cerebrospinal fluid tau and amyloid-β levels3, structural and functional magnetic resonance imaging4 and the recent use of brain amyloid imaging5 or inflammaging6, are limited because they are either invasive, time-consuming or expensive. Blood-based biomarkers may be a more attractive option, but none can currently detect preclinical Alzheimer's disease with the required sensitivity and specificity7. Herein, we describe our lipidomic approach to detecting preclinical Alzheimer's disease in a group of cognitively normal older adults. We discovered and validated a set of ten lipids from peripheral blood that predicted phenoconversion to either amnestic mild cognitive impairment or Alzheimer's disease within a 2–3 year timeframe with over 90% accuracy. This biomarker panel, reflecting cell membrane integrity, may be sensitive to early neurodegeneration of preclinical Alzheimer's disease.

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Figure 1: Memory composite z-scores and trend plots for the ten-metabolite panel in the discovery phase.
Figure 2: ROC results for the lipidomics analyses.

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  • 20 June 2014

     In the version of this article initially published online, the Source Data file for Figure 1 contained a transposition error that occurred when the authors were moving data from their analysis software into Excel. This error does not affect the accuracy of the data shown in Figure 1. This error has been corrected in the HTML version of the article.


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We thank E. Johnson and D. Greenia for study coordination; P. Bailie, M. Patel and A. Balasubramanian for assistance with data collection; and A. Almudevar for statistical support. We also thank R. Padilla and I. Conteh for processing the blood samples and R. Singh and P. Kaur for technical assistance in developing the lipidomics data. This work was funded by US National Institutes of Health grants R01AG030753 and DOD W81XWH-09-1-0107 to H.J.F.

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Authors and Affiliations



H.J.F., T.R.M., C.H.K., W.J.H., S.G.F., M.M., M.S.F. and A.K.C. conceived of the study. W.J.H., J.M.H., M.D.N., S.A.R. and C.H.K. recruited participants and provided material support for data collection. M.M., D.J.B. and C.B.P. collected the clinical data. D.R.P., S.G.F. and M.M. derived the cognitive z-score methodology. M.M. completed statistical analysis of the cognitive data. A.K.C., M.S.F., T.R.M. and L.H.M. completed the lipidomics analyses. M.T.T., X.Z. and A.K.C. completed statistical analysis of the lipidomics data. M.M., A.K.C., M.S.F. and H.J.F. wrote the manuscript. All authors edited the manuscript for content.

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Correspondence to Howard J Federoff.

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The authors declare no competing financial interests.

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Mapstone, M., Cheema, A., Fiandaca, M. et al. Plasma phospholipids identify antecedent memory impairment in older adults. Nat Med 20, 415–418 (2014).

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