Elevated Stearoyl-CoA Desaturase in Brains of Patients with Alzheimers Disease 英文参考文献.docVIP

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Elevated Stearoyl-CoA Desaturase in Brains of Patients with Alzheimers Disease 英文参考文献.doc

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Elevated Stearoyl-CoA Desaturase in Brains of Patients with Alzheimers Disease 英文参考文献

ElevatedStearoyl-CoADesaturaseinBrainsofPatients withAlzheimer’sDisease GiuseppeAstarita1,2,Kwang-MookJung1,VitalyVasilevko3,NicholasV.DiPatrizio1,SarahK.Martin4, DavidH.Cribbs3,ElizabethHead4,CarlW.Cotman3,DanielePiomelli1,2,5* 1DepartmentofPharmacology,UniversityofCaliforniaIrvine,Irvine,California,UnitedStatesofAmerica,2UnitofDrugDiscoveryandDevelopment,ItalianInstituteof Technology, Genoa, Italy, 3Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, California, United States of America, 4Sanders-BrownCenteronAging,UniversityofKentucky,Lexington,Kentucky,UnitedStatesofAmerica,5DepartmentofBiologicalChemistry,UniversityofCalifornia Irvine,Irvine,California,UnitedStatesofAmerica Abstract The molecular bases of Alzheimer’s disease (AD) remain unclear. We used a lipidomic approach to identify lipid abnormalitiesinthebrainsofsubjectswithAD(N=37)comparedtoage-matchedcontrols(N=17).Theanalysesrevealed statisticallydetectableelevationsinlevelsofnon-esterifiedmonounsaturatedfattyacids(MUFAs)andmeadacid(20:3n-9)in mid-frontalcortex,temporalcortexandhippocampusofADpatients.FurtherstudiesshowedthatbrainmRNAsencoding forisoformsoftherate-limitingenzymeinMUFAsbiosynthesis,stearoyl-CoAdesaturase(SCD-1,SCD-5aandSCD-5b),were elevated in subjects withAD. The monounsaturated/saturated fatty acid ratio (‘desaturation index’) – displayed astrong negative correlation with measures of cognition: the Mini Mental State Examination test (r=20.80; P=0.0001) and the BostonNamingtest(r=20.57;P=0.0071).OurresultsrevealapreviouslyunrecognizedroleforthelipogenicenzymeSCD inAD. Citation: Astarita G, Jung K-M, Vasilevko V, DiPatrizio NV, Martin SK, et al. (2011) Elevated Stearoyl-CoA Desaturase in Brains of Patients with Alzheimer’s Disease.PLoSONE6(10):e24777.doi:10.1371/journal.pone.0024777 Editor:SilvanaGaetani,SapienzaUniversityofRome,Italy ReceivedJune21,2011;AcceptedAugust17,2011;PublishedOctober26,2011 Copyright: ? 2011 Astarita et al. Thi