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Non-targeted lipidomics of CSF and frontal cortex grey and white matter in control, mild cognitive impairment, and Alzheimer’s disease subjects

Published online by Cambridge University Press:  10 April 2015

Paul L. Wood ,
Brooke L. Barnette ,
Jeffrey A. Kaye ,
Joseph F. Quinn  and
Randall L. Woltjer
Paul L. Wood*
Affiliation:
Metabolomics Unit, Department of Physiology and Pharmacology, DeBusk College of Osteopathic Medicine, Lincoln Memorial University, Harrogate, TN, USA
Brooke L. Barnette
Affiliation:
Metabolomics Unit, Department of Physiology and Pharmacology, DeBusk College of Osteopathic Medicine, Lincoln Memorial University, Harrogate, TN, USA
Jeffrey A. Kaye
Affiliation:
Department of Neurology, Portland VA Medical Center, Oregon Health Science University, Portland, OR, USA
Joseph F. Quinn
Affiliation:
Department of Neurology, Portland VA Medical Center, Oregon Health Science University, Portland, OR, USA
Randall L. Woltjer
Affiliation:
Department of Neurology, Portland VA Medical Center, Oregon Health Science University, Portland, OR, USA
*
Paul L. Wood, Metabolomics Unit, Department of Physiology and Pharmacology, DeBusk College of Osteopathic Medicine, Lincoln Memorial University, 6965 Cumberland Gap Parkway, Harrogate, TN 37752, USA Tel: 423-869-6666; Fax: 423-869-7174; E-mail: [email protected]
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Abstract

Objective

We undertook a non-targeted lipidomics analysis of post-mortem cerebrospinal fluid (CSF), frontal cortex grey matter, and subjacent white matter to define potential biomarkers that distinguish cognitively intact subjects from those with incipient or established dementia. Our objective was to increase our understanding of the role of brain lipids in pathophysiology of aging and age-related cognitive impairment.

Methods

Levels of 650 individual lipids, across 26 lipid subclasses, were measured utilising a high-resolution mass spectrometric analysis platform.

Results

Monoacylglycerols (MAG), diacylglycerols (DAG), and the very-long-chain fatty acid 26:0 were elevated in the grey matter of the mild cognitive impairment (MCI) and old dementia (OD) cohorts. Ethanolamine plasmalogens (PlsEtn) were decreased in the grey matter of the young dementia (YD) and OD cohorts while and phosphatidylethanolamines (PtdEth) were lower in the MCI, YD and OD cohorts. In the white matter, decrements in sulphatide levels were detected in the YD group, DAG levels were elevated in the MCI group, and MAG levels were increased in the YD and OD groups.

Conclusion

The parallel changes in grey matter MAGs and DAGs in the MCI and OD groups suggest that these two cohorts may have a similar underlying pathophysiology; consistent with this, MCI subjects were more similar in age to OD than to YD subjects. While PlsEtn and phosphatidylethanolamine were decreased in the YD and OD groups they were unaltered in the MCI group indicating that alterations in plasmalogen synthesis are unlikely to represent an initiating event in the transition from MCI to dementia.

Keywords

Alzheimer’s diseaselipidomicsdiacylglycerolsmild cognitive impairmentfrontal cortex
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 27 , Issue 5 , October 2015 , pp. 270 - 278
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Copyright
© Scandinavian College of Neuropsychopharmacology 2015 

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