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Open AccessArticle

Oxylipin Profiling of Alzheimer’s Disease in Nondiabetic and Type 2 Diabetic Elderly

Department of Neurology, University of Kansas Alzheimer’s Disease Center, Kansas City, KS 66205, USA
University of Kansas Alzheimer’s Disease Center, Fairway, KS 66205, USA
Arkansas Children’s Nutrition Center, Little Rock, AR 72205, USA
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
Department of Molecular and Integrative Physiology, University of Kansas, Kansas City, KS 66045, USA
Kansas City VA Medical Center, Kansas City, MO 64128, USA
Author to whom correspondence should be addressed.
Metabolites 2019, 9(9), 177;
Received: 2 August 2019 / Revised: 27 August 2019 / Accepted: 3 September 2019 / Published: 5 September 2019
Oxygenated lipids, called “oxylipins,” serve a variety of important signaling roles within the cell. Oxylipins have been linked to inflammation and vascular function, and blood patterns have been shown to differ in type 2 diabetes (T2D). Because these factors (inflammation, vascular function, diabetes) are also associated with Alzheimer’s disease (AD) risk, we set out to characterize the serum oxylipin profile in elderly and AD subjects to understand if there are shared patterns between AD and T2D. We obtained serum from 126 well-characterized, overnight-fasted elderly individuals who underwent a stringent cognitive evaluation and were determined to be cognitively healthy or AD. Because the oxylipin profile may also be influenced by T2D, we assessed nondiabetic and T2D subjects separately. Within nondiabetic individuals, cognitively healthy subjects had higher levels of the nitrolipid 10-nitrooleate (16.8% higher) compared to AD subjects. AD subjects had higher levels of all four dihydroxyeicosatrienoic acid (DiHETrE) species: 14,15-DiHETrE (18% higher), 11,12 DiHETrE (18% higher), 8,9-DiHETrE (23% higher), and 5,6-DiHETrE (15% higher). Within T2D participants, we observed elevations in 14,15-dihydroxyeicosa-5,8,11-trienoic acid (14,15-DiHETE; 66% higher), 17,18-dihydroxyeicosa-5,8,11,14-tetraenoic acid (17,18-DiHETE; 29% higher) and 17-hydroxy-4,7,10,13,15,19-docosahexaenoic acid (17-HDoHE; 105% higher) and summed fatty acid diols (85% higher) in subjects with AD compared to cognitively healthy elderly, with no differences in the DiHETrE species between groups. Although these effects were no longer significant following stringent adjustment for multiple comparisons, the consistent effects on groups of molecules with similar physiological roles, as well as clear differences in the AD-related profiles within nondiabetic and T2D individuals, warrant further research into these molecules in the context of AD. View Full-Text
Keywords: oxylipin; alzheimer’s disease; type 2 diabetes; dihetre oxylipin; alzheimer’s disease; type 2 diabetes; dihetre
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Morris, J.K.; Piccolo, B.D.; John, C.S.; Green, Z.D.; Thyfault, J.P.; Adams, S.H. Oxylipin Profiling of Alzheimer’s Disease in Nondiabetic and Type 2 Diabetic Elderly. Metabolites 2019, 9, 177.

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