title: Targeted Lipidomics of Fontal Cortex and Plasma Diacylglycerols (DAG) in Mild Cognitive Impairment and Alzheimer's Disease: Validation of DAG Accumulation Early in the Pathophysiology of Alzheimer's Disease.
abstract: Previous studies have demonstrated augmented levels of diacylglycerols (DAG) in the frontal cortex and plasma of Alzheimer's disease (AD) patients. We extended these findings from non-targeted lipidomics studies to design a lipidomics platform to interrogate DAGs and monoacylglycerols (MAG) in the frontal cortex and plasma of MCI subjects. Control subjects included both aged normal controls and controls with normal cognition, but AD pathology at autopsy, individuals termed non-demented AD neuropathology. DAGs with saturated, unsaturated, and polyunsaturated fatty acid substituents were found to be elevated in MCI frontal cortex and plasma. Tandem mass spectrometry of the DAGs did not reveal any differences in the distributions of the fatty acid substitutions between MCI and control subjects. While triacylglycerols were not altered in MCI subjects there were increases in MAG levels both in the frontal cortex and plasma. In toto, increased levels of DAGs and MAGs appear to occur early in AD pathophysiology and require both further validation in a larger patient cohort and elucidation of the lipidomics alteration(s) that lead to the accumulation of DAGs in MCI subjects.
authors.affiliation: Lipidomics Unit, Department of Physiology and Pharmacology, DeBusk College of Osteopathic Medicine, Lincoln Memorial University, Harrogate, TN, USA.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Wood
authors.affiliation: Lipidomics Unit, Department of Physiology and Pharmacology, DeBusk College of Osteopathic Medicine, Lincoln Memorial University, Harrogate, TN, USA.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Medicherla
authors.affiliation: Lipidomics Unit, Department of Physiology and Pharmacology, DeBusk College of Osteopathic Medicine, Lincoln Memorial University, Harrogate, TN, USA.
authors.forename: Naveen
authors.initials: N
authors.lastname: Sheikh
authors.affiliation: Lipidomics Unit, Department of Physiology and Pharmacology, DeBusk College of Osteopathic Medicine, Lincoln Memorial University, Harrogate, TN, USA.
authors.forename: Bradley
authors.initials: B
authors.lastname: Terry
authors.affiliation: Lipidomics Unit, Department of Physiology and Pharmacology, DeBusk College of Osteopathic Medicine, Lincoln Memorial University, Harrogate, TN, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Phillipps
authors.affiliation: Department of Neurology, Oregon Health Science University and Portland VA Medical Center, Portland, OR, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kaye
authors.affiliation: Department of Neurology, Oregon Health Science University and Portland VA Medical Center, Portland, OR, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Quinn
authors.affiliation: Department of Neurology, Oregon Health Science University and Portland VA Medical Center, Portland, OR, USA.
authors.forename: Randall L
authors.initials: RL
authors.lastname: Woltjer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000378:metabolism*; D004075:Diglycerides / Q000097:blood*; D005625:Frontal Lobe / Q000378:metabolism*; D006801:Humans; D008609:Mental Status Schedule; D008875:Middle Aged; D050178:Monoglycerides / Q000097:blood; D053719:Tandem Mass Spectrometry
chemical_list: D004075:Diglycerides; D050178:Monoglycerides
keywords: Alzheimer’s disease; diacylglycerols; mild cognitive impairment; monoacylglycerols