Sphingomyelin SM(d18:1/18:0) is Significantly Enhanced in Cerebrospinal Fluid Samples Dichotomized by Pathological Amyloid-β42, Tau, and Phospho-Tau-181 Levels
作者： Georg Kemmler , Christian Humpel , Therese Koal , Kristaps Klavins , Daniele Seppi
DOI: 10.3233/JAD-142319
关键词:
摘要: Alzheimer’s disease (AD) is a severe and chronic neurodegenerative disorder of the brain. The laboratory diagnosis limited to analysis three biomarkers in cerebrospinal fluid (CSF): amyloid-β42 (Aβ42), total tau, phospho-tau-181 (P-tau-181). However, there need find more CSF that can improve sensitivity specificity. aim present study was analyze endogenous small metabolites (metabolome) CSF, which may provide potentially new insights into biochemical processes involved AD. One hundred samples were dichotomized by normal (n = 50) pathological decreased Aβ42 increased tau P-tau-181 levels 50; correlating an AD-like pathology). These analyzed using AbsoluteIDQ® p180 Kit (BIOCRATES Life Sciences), included 40 acylcarnitines, 21 amino acids, 19 biogenic amines, 15 sphingolipids, 90 glycerophospholipids. Our data show two sphingomyelins (SM (d18:1/18:0) SM (d18:1/18:1)), 5 glycerophospholipids (PC aa C32:0, PC C34:1, C36:1, C38:4 C38:6), 1 acylcarnitine (C3-DC-M/C5-OH) significantly altered with “AD-like pathology”. Sphingomyelin proved be specific (76%) sensitive (66%) biomarker defined cut-off 546 nM. Correct diagnoses for out 32 unknown could achieved this value. In conclusion, sphingolipid patients displaying Aβ42, P-tau-181.
sci-hub.se 参考文章(29)
George Perry, Akihiko Nunomura, Arun K. Raina, Gjumrakch Aliev, Sandra L. Siedlak, Peggy L. R. Harris, Gemma Casadesus, Robert B. Petersen, William Bligh‐Glover, Elizabeth Balraj, Grace J. Petot, Mark A. Smith, A metabolic basis for Alzheimer disease. Neurochemical Research. ,vol. 28, pp. 1549- 1552 ,(2003) , 10.1023/A:1025678510480
Eric Vittinghoff, Charles E. McCulloch, David V. Glidden, Stephen C. Shiboski, 5 Linear and Non-Linear Regression Methods in Epidemiology and Biostatistics Handbook of Statistics. ,vol. 27, pp. 148- 186 ,(2007) , 10.1016/S0169-7161(07)27005-1
R.T. Dobrowsky, C. Kamibayashi, M.C. Mumby, Y.A. Hannun, Ceramide activates heterotrimeric protein phosphatase 2A. Journal of Biological Chemistry. ,vol. 268, pp. 15523- 15530 ,(1993) , 10.1016/S0021-9258(18)82288-8
Radhia Mahfoud, Nicolas Garmy, Marc Maresca, Nouara Yahi, Antoine Puigserver, Jacques Fantini, Identification of a Common Sphingolipid-binding Domain in Alzheimer, Prion, and HIV-1 Proteins Journal of Biological Chemistry. ,vol. 277, pp. 11292- 11296 ,(2002) , 10.1074/JBC.M111679200
A. Fiedorowicz, S. Prokopiuk, M. Żendzian-Piotrowska, A. Chabowski, H. Car, Sphingolipid profiles are altered in prefrontal cortex of rats under acute hyperglycemia Neuroscience. ,vol. 256, pp. 282- 291 ,(2014) , 10.1016/J.NEUROSCIENCE.2013.10.022
Irfan Y. Tamboli, Nguyen T. Tien, Jochen Walter, Sphingolipid storage impairs autophagic clearance of Alzheimer-associated proteins Autophagy. ,vol. 7, pp. 645- 646 ,(2011) , 10.4161/AUTO.7.6.15122
Mark Mapstone, Amrita K Cheema, Massimo S Fiandaca, Xiaogang Zhong, Timothy R Mhyre, Linda H MacArthur, William J Hall, Susan G Fisher, Derick R Peterson, James M Haley, Michael D Nazar, Steven A Rich, Dan J Berlau, Carrie B Peltz, Ming T Tan, Claudia H Kawas, Howard J Federoff, Plasma phospholipids identify antecedent memory impairment in older adults Nature Medicine. ,vol. 20, pp. 415- 418 ,(2014) , 10.1038/NM.3466
C.L. Grady, J.V. Haxby, B. Horwitz, G. Berg, S.I. Rapoport, Neuropsychological and cerebral metabolic function in early vs late onset dementia of the Alzheimer type. Neuropsychologia. ,vol. 25, pp. 807- 816 ,(1987) , 10.1016/0028-3932(87)90118-7
Paula I. Moreira, Xiongwei Zhu, Hyoung-Gon Lee, Kazuhiro Honda, Mark A. Smith, George Perry, The (un)balance between metabolic and oxidative abnormalities and cellular compensatory responses in Alzheimer disease. Mechanisms of Ageing and Development. ,vol. 127, pp. 501- 506 ,(2006) , 10.1016/J.MAD.2006.01.024
Thomas Illig, Christian Gieger, Guangju Zhai, Werner Römisch-Margl, Rui Wang-Sattler, Cornelia Prehn, Elisabeth Altmaier, Gabi Kastenmüller, Bernet S Kato, Hans-Werner Mewes, Thomas Meitinger, Martin Hrabé de Angelis, Florian Kronenberg, Nicole Soranzo, H-Erich Wichmann, Tim D Spector, Jerzy Adamski, Karsten Suhre, A genome-wide perspective of genetic variation in human metabolism Nature Genetics. ,vol. 42, pp. 137- 141 ,(2010) , 10.1038/NG.507