title: Increased ceramide in brains with Alzheimer's and other neurodegenerative diseases.
abstract: Ceramide has been suggested to participate in the neuronal cell death that leads to Alzheimer's disease (AD), but its role is not yet well-understood. We compared the levels of six ceramide subspecies, which differ in the length of their fatty acid moieties, in brains from patients who suffered from AD, other neuropathological disorders, or both. We found elevated levels of Cer16, Cer18, Cer20, and Cer24 in brains from patients with any of the tested neural defects. Moreover, ceramide levels were highest in patients with more than one neuropathologic abnormality. Interestingly, the range of values was higher among brains with neural defects than in controls, suggesting that the regulation of ceramide synthesis is normally under tight control, and that this tight control may be lost during neurodegeneration. These changes, however, did not alter the ratio between the tested ceramide species. To explore the mechanisms underlying this dysregulation, we evaluated the expression of four genes connected to ceramide metabolism: ASMase, NSMase 2, GALC, and UGCG. The patterns of gene expression were complex, but overall, ASMase, NSMase 2, and GALC were upregulated in specimens from patients with neuropathologic abnormalities in comparison with age-matched controls. Such findings suggest these genes as attractive candidates both for diagnostic purposes and for intervening in neurodegenerative processes.
authors.affiliation: Loma Linda University, Department of Basic Science, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA.
authors.forename: Valery
authors.initials: V
authors.lastname: Filippov
authors.forename: Minwoo Andrew
authors.initials: MA
authors.lastname: Song
authors.forename: Kangling
authors.initials: K
authors.lastname: Zhang
authors.forename: Harry V
authors.initials: HV
authors.lastname: Vinters
authors.forename: Spencer
authors.initials: S
authors.lastname: Tung
authors.forename: Wolff M
authors.initials: WM
authors.lastname: Kirsch
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Penelope J
authors.initials: PJ
authors.lastname: Duerksen-Hughes
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D002518:Ceramides / Q000235:genetics / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D005698:Galactosylceramidase / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D019636:Neurodegenerative Diseases / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D002518:Ceramides; D012333:RNA, Messenger; C491484:SMPD3 protein, human; D013108:Sphingomyelin Phosphodiesterase; D005698:Galactosylceramidase