Elevated Stearoyl-CoA Desaturase in Brains of Patients with Alzheimer's Disease

• Published in: PloS one Vol. 6; no. 10; p. e24777
• Main Authors: Astarita, Giuseppe, Jung, Kwang-Mook, Vasilevko, Vitaly, DiPatrizio, Nicholas V., Martin, Sarah K., Cribbs, David H., Head, Elizabeth, Cotman, Carl W., Piomelli, Daniele
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.10.2011; Public Library of Science (PLoS)
• Subjects: 8,11,14-Eicosatrienoic Acid - analogs & derivatives; 8,11,14-Eicosatrienoic Acid - analysis; Abnormalities; Advertising executives; Age; Aged; Aged, 80 and over; Aging; Alzheimer Disease - enzymology; Alzheimer Disease - etiology; Alzheimer's disease; Alzheimers disease; Analysis; Biology; Biosynthesis; Bipolar disorder; Brain; Brain - metabolism; Brain Mapping; Case-Control Studies; Chromatography; Cognition; Correlation analysis; Cortex (frontal); Cortex (temporal); Desaturase; Desaturation; Enzymes; Esterification; Fatty acids; Fatty Acids, Monounsaturated - analysis; Female; Gene expression; Humans; Insulin; Isoforms; Lipids; Male; Mass spectrometry; Medical research; Medicine; Memory; Metabolic Networks and Pathways; Metabolism; Monounsaturated fatty acids; Neurodegenerative diseases; Neurological disorders; Neuropathology; Obesity; Patients; Pharmacology; Protein Isoforms - analysis; RNA, Messenger - analysis; Rodents; Scientific imaging; Statistical analysis; Stearoyl-CoA desaturase; Stearoyl-CoA Desaturase - genetics; Stearoyl-CoA Desaturase - metabolism; Temporal lobe; United States > US; Kentucky; California
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0024777

The molecular bases of Alzheimer's disease (AD) remain unclear. We used a lipidomic approach to identify lipid abnormalities in the brains of subjects with AD (N = 37) compared to age-matched controls (N = 17). The analyses revealed statistically detectable elevations in levels of non-esterified monounsaturated fatty acids (MUFAs) and mead acid (20:3n-9) in mid-frontal cortex, temporal cortex and hippocampus of AD patients. Further studies showed that brain mRNAs encoding for isoforms of the rate-limiting enzyme in MUFAs biosynthesis, stearoyl-CoA desaturase (SCD-1, SCD-5a and SCD-5b), were elevated in subjects with AD. The monounsaturated/saturated fatty acid ratio ('desaturation index')--displayed a strong negative correlation with measures of cognition: the Mini Mental State Examination test (r = -0.80; P = 0.0001) and the Boston Naming test (r = -0.57; P = 0.0071). Our results reveal a previously unrecognized role for the lipogenic enzyme SCD in AD.