elevated stearoyl-coa desaturase in brains of patients with alzheimers disease高架stearoyl-coa desaturase老年痴呆症患者的大脑.pdfVIP

Elevated Stearoyl-CoA Desaturase in Brains of Patients with Alzheimer’s Disease 1,2 1 3 1 4 Giuseppe Astarita , Kwang-Mook Jung , Vitaly Vasilevko , Nicholas V. DiPatrizio , Sarah K. Martin , 3 4 3 1,2,5 David H. Cribbs , Elizabeth Head , Carl W. Cotman , Daniele Piomelli * 1 Department of Pharmacology, University of California Irvine, Irvine, California, United States of America, 2 Unit of Drug Discovery and Development, Italian Institute of Technology, Genoa, Italy, 3 Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, California, United States of America, 4 Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, United States of America, 5 Department of Biological Chemistry, University of California Irvine, Irvine, California, United States of America Abstract 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 str