Could plasma sphingolipids be diagnostic or prognostic biomarkers for Alzheimer’s disease?

References

• Alzheimer’s Disease International. World Alzheimer Report 2009 Executive Summary. London, UK (2009).
   Google Scholar
• Pimplikar SW, Nixon RA, Robakis NK, Shen J, Tsai LH. Amyloid-independent mechanisms in Alzheimer’s disease pathogenesis. J. Neurosci. 30(45), 14946–14954 (2010).
   Google Scholar
• Mielke MM, Lyketsos CG. Lipids and the pathogenesis of Alzheimer’s disease: is there a link? Int. Rev. Psychiatry 18(2), 173–186 (2006).
   Google Scholar
• Lütjohann D, Meichsner S, Pettersson H. Lipids in Alzheimer’s disease and their potential for therapy. Clin. Lipidol. 7(1), 65–78 (2012).
   Google Scholar
• Haughey NJ, Bandaru VV, Bae M, Mattson MP. Roles for dysfunctional sphingolipid metabolism in Alzheimer’s disease neuropathogenesis. Biochim. Biophys. Acta 1801(8), 878–886 (2010).
   Google Scholar
• France-Lanord V, Brugg B, Michel PP, Agid Y, Ruberg M. Mitochondrial free radical signal in ceramide-dependent apoptosis: a putative mechanism for neuronal death in Parkinson’s disease. J. Neurochem. 69(4), 1612–1621 (1997).
   Google Scholar
• Cutler RG, Pedersen WA, Camandola S, Rothstein JD, Mattson MP. Evidence that accumulation of ceramides and cholesterol esters mediates oxidative stress-induced death of motor neurons in amyotrophic lateral sclerosis. Ann. Neurol. 52(4), 448–457 (2002).
   Google Scholar
• Cutler RG, Kelly J, Storie K et al. Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer’s disease. Proc. Natl Acad. Sci. USA 101(7), 2070–2075 (2004). ▪▪ Describes how ceramides may mediate the relationship between amyloid-b deposition and neurodegeneration.
   Google Scholar
• Haughey NJ, Cutler RG, Tamara A et al. Perturbation of sphingolipid metabolism and ceramide production in HIV-dementia. Ann. Neurol. 55(2), 257–267 (2004).
   Google Scholar
• Mielke MM, Bandaru VV, Haughey NJ, Rabins PV, Lyketsos CG, Carlson MC. Serum sphingomyelins and ceramides are early predictors of memory impairment. Neurobiol. Aging 31(1), 17–24 (2010).
   Google Scholar
• Mielke MM, Bandaru VV, McArthur JC, Chu M, Haughey NJ. Disturbance in cerebral spinal fluid sphingolipid content is associated with memory impairment in subjects infected with the human immunodeficiency virus. J. Neurovirol. 16(6), 445–456 (2010).
   Google Scholar
• Merrill AH Jr, Jones DD. An update of the enzymology and regulation of sphingomyelin metabolism. Biochim. Biophys. Acta 1044(1), 1–12 (1990).
   Google Scholar
• Slotte JP. Cholesterol-sphingomyelin interactions in cells – effects on lipid metabolism. Subcell. Biochem. 28, 277–293 (1997).
   Google Scholar
• Brown DA, London E. Structure and function of sphingolipid- and cholesterol-rich membrane rafts. J. Biol. Chem. 275(23), 17221–17224 (2000).
   Google Scholar
• Andrieu-Abadie N, Gouaze V, Salvayre R, Levade T. Ceramide in apoptosis signaling: relationship with oxidative stress. Free Radic. Biol. Med. 31(6), 717–728 (2001).
   Google Scholar
• Goodman Y, Mattson MP. Ceramide protects hippocampal neurons against excitotoxic and oxidative insults, and amyloid b-peptide toxicity. J. Neurochem. 66(2), 869–872 (1996).
   Google Scholar
• Hannun YA. Functions of ceramide in coordinating cellular responses to stress. Science 274(5294), 1855–1859 (1996).
   Google Scholar
• Ariga T, McDonald MP, Yu RK. Role of ganglioside metabolism in the pathogenesis of Alzheimer’s disease – a review. J. Lipid Res. 49(6), 1157–1175 (2008).
   Google Scholar
• Ohsawa T. Changes of mouse brain gangliosides during aging from young adult until senescence. Mech. Ageing Dev. 50(2), 169–177 (1989).
   Google Scholar
• Svennerholm L, Bostrom K, Jungbjer B, Olsson L. Membrane lipids of adult human brain: lipid composition of frontal and temporal lobe in subjects of age 20 to 100 years. J. Neurochem. 63(5), 1802–1811 (1994).
   Google Scholar
• Mattson MP, Cutler RG, Jo DG. Alzheimer peptides perturb lipid-regulating enzymes. Nat. Cell Biol. 7(11), 1045–1047 (2005). ▪▪ Effectively summarizes the relationships between ceramides and amyloid-b.
   Google Scholar
• Jana A, Pahan K. Human immunodeficiency virus type 1 gp120 induces apoptosis in human primary neurons through redoxregulated activation of neutral sphingomyelinase. J. Neurosci. 24(43), 9531–9540 (2004).
   Google Scholar
• Lee JT, Xu J, Lee JM et al. Amyloid-b peptide induces oligodendrocyte death by activating the neutral sphingomyelinase–ceramide pathway. J. Cell Biol. 164(1), 123–131 (2004).
   Google Scholar
• Grimm MO, Grimm HS, Patzold AJ et al. Regulation of cholesterol and sphingomyelin metabolism by amyloid-b and presenilin. Nat. Cell Biol. 7(11), 1118–1123 (2005).
   Google Scholar
• Gulbins E, Kolesnick R. Raft ceramide in molecular medicine. Oncogene 22(45), 7070–7077 (2003).
   Google Scholar
• Puglielli L, Ellis BC, Saunders AJ, Kovacs DM. Ceramide stabilizes b-site amyloid precursor protein cleaving enzyme 1 and promotes amyloid b-peptide biogenesis. J. Biol. Chem. 278(22), 19777–19783 (2003).
   Google Scholar
• Kalvodova L, Kahya N, Schwille P et al. Lipids as modulators of proteolytic activity of BACE: involvement of cholesterol, glycosphingolipids, and anionic phospholipids in vitro. J. Biol. Chem. 280(44), 36815–36823 (2005).
   Google Scholar
• Yanagisawa K. Role of gangliosides in Alzheimer’s disease. Biochim. Biophys. Acta 1768(8), 1943–1951 (2007).
   Google Scholar
• Yanagisawa K, Odaka A, Suzuki N, Ihara Y. GM1 ganglioside-bound amyloid b-protein (A b): a possible form of preamyloid in Alzheimer’s disease. Nat. Med. 1(10), 1062–1066 (1995).
   Google Scholar
• Hayashi H, Kimura N, Yamaguchi H et al. A seed for Alzheimer amyloid in the brain. J. Neurosci. 24(20), 4894–4902 (2004).
   Google Scholar
• Yamamoto N, Hirabayashi Y, Amari M et al. Assembly of hereditary amyloid b-protein variants in the presence of favorable gangliosides. FEBS Lett. 579(10), 2185–2190 (2005).
   Google Scholar
• Yamamoto N, Matsubara E, Maeda S et al. A ganglioside-induced toxic soluble Ab assembly. Its enhanced formation from Ab bearing the Arctic mutation. J. Biol. Chem. 282(4), 2646–2655 (2007).
   Google Scholar
• Oikawa N, Yamaguchi H, Ogino K et al. Gangliosides determine the amyloid pathology of Alzheimer’s disease. Neuroreport 20(12), 1043–1046 (2009).
   Google Scholar
• Eckert GP, Muller WE. Presenilin 1 modifies lipid raft composition of neuronal membranes. Biochem. Biophys. Res. Commun. 382(4), 673–677 (2009).
   Google Scholar
• Takasugi N, Sasaki T, Suzuki K et al. BACE1 activity is modulated by cell-associated sphingosine-1-phosphate. J. Neurosci. 31(18), 6850–6857 (2011).
   Google Scholar
• Goedert M, Jakes R, Qi Z, Wang JH, Cohen P. Protein phosphatase 2A is the major enzyme in brain that dephosphorylates tau protein phosphorylated by proline-directed protein kinases or cyclic AMP-dependent protein kinase. J. Neurochem. 65(6), 2804–2807 (1995).
   Google Scholar
• Gong CX, Grundke-Iqbal I, Iqbal K. Dephosphorylation of Alzheimer’s disease abnormally phosphorylated tau by protein phosphatase-2A. Neuroscience 61(4), 765–772 (1994).
   Google Scholar
• Chalfant CE, Kishikawa K, Mumby MC, Kamibayashi C, Bielawska A, Hannun YA. Long chain ceramides activate protein phosphatase-1 and protein phosphatase-2A. Activation is stereospecific and regulated by phosphatidic acid. J. Biol. Chem. 274(29), 20313–20317 (1999).
   Google Scholar
• Dobrowsky RT, Kamibayashi C, Mumby MC, Hannun YA. Ceramide activates heterotrimeric protein phosphatase 2A. J. Biol. Chem. 268(21), 15523–15530 (1993).
   Google Scholar
• Mukhopadhyay A, Saddoughi SA, Song P et al. Direct interaction between the inhibitor 2 and ceramide via sphingolipidprotein binding is involved in the regulation of protein phosphatase 2A activity and signaling. FASEB J. 23(3), 751–763 (2009). ▪ Describes a mechanism by which ceramide may regulate tau phosphorylation.
   Google Scholar
• Oddo S, Caccamo A, Tran L et al. Temporal profile of amyloid-b (Ab) oligomerization in an in vivo model of Alzheimer disease. A link between Ab and tau pathology. J. Biol. Chem. 281(3), 1599–1604 (2006).
   Google Scholar
• Arboleda G, Morales LC, Benitez B, Arboleda H. Regulation of ceramide-induced neuronal death: cell metabolism meets neurodegeneration. Brain Res. Rev. 59(2), 333–346 (2009).
   Google Scholar
• Hannun YA, Luberto C. Ceramide in the eukaryotic stress response. Trends Cell Biol. 10(2), 73–80 (2000).
   Google Scholar
• de la Monte SM. Triangulated mal-signaling in Alzheimer’s disease: roles of neurotoxic ceramides, ER stress, and insulin resistance reviewed. J. Alzheimers Dis. 30, S231–S249 (2012).
   Google Scholar
• Zhang Z, Zhao R, Qi J, Wen S, Tang Y, Wang D. Inhibition of glycogen synthase kinase-3b by Angelica sinensis extract decreases b-amyloid-induced neurotoxicity and tau phosphorylation in cultured cortical neurons. J. Neurosci. Res. 89(3), 437–447 (2011).
   Google Scholar
• He X, Huang Y, Li B, Gong CX, Schuchman EH. Deregulation of sphingolipid metabolism in Alzheimer’s disease. Neurobiol. Aging 31(3), 398–408 (2010).
   Google Scholar
• Barrier L, Ingrand S, Fauconneau B, Page G. Gender-dependent accumulation of ceramides in the cerebral cortex of the APP(SL)/PS1Ki mouse model of Alzheimer’s disease. Neurobiol. Aging 31(11), 1843–1853 (2010).
   Google Scholar
• Barrier L, Fauconneau B, Noel A, Ingrand S. Ceramide and related-sphingolipid levels are not altered in disease-associated brain regions of APP and APP/PS1 mouse models of Alzheimer’s disease: relationship with the lack of neurodegeneration? Int. J. Alzheimers Dis. 920958 (2011).
   Google Scholar
• Cheng H, Zhou Y, Holtzman DM, Han X. Apolipoprotein E mediates sulfatide depletion in animal models of Alzheimer’s disease. Neurobiol. Aging 31(7), 1188–1196 (2010).
   Google Scholar
• Cuvillier O, Pirianov G, Kleuser B et al. Suppression of ceramide-mediated programmed cell death by sphingosine-1-phosphate. Nature 381(6585), 800–803 (1996).
   Google Scholar
• Mielke MM, Lyketsos CG. Alterations of the sphingolipid pathway in Alzheimer’s disease: new biomarkers and treatment targets? Neuromolecular Med. 12(4), 331–340 (2010).
   Google Scholar
• Pettegrew JW, Panchalingam K, Hamilton RL, McClure RJ. Brain membrane phospholipid alterations in Alzheimer’s disease. Neurochem. Res. 26(7), 771–782 (2001).
   Google Scholar
• Han X, Holtzman DM, McKeel DW Jr, Kelley J, Morris JC. Substantial sulfatide deficiency and ceramide elevation in very early Alzheimer’s disease: potential role in disease pathogenesis. J. Neurochem. 82(4), 809–818 (2002). ▪ Describes, for the first time, the perturbations of sulfatides and ceramides in postmortem brains of early Alzheimer’s disease cases.
   Google Scholar
• Huang Y, Tanimukai H, Liu F, Iqbal K, Grundke-Iqbal I, Gong CX. Elevation of the level and activity of acid ceramidase in Alzheimer’s disease brain. Eur. J. Neurosci. 20(12), 3489–3497 (2004).
   Google Scholar
• Katsel P, Li C, Haroutunian V. Gene expression alterations in the sphingolipid metabolism pathways during progression of dementia and Alzheimer’s disease: a shift toward ceramide accumulation at the earliest recognizable stages of Alzheimer’s disease? Neurochem. Res. 32(4–5), 845–856 (2007).
   Google Scholar
• Bandaru VV, Troncoso J, Wheeler D et al. ApoE4 disrupts sterol and sphingolipid metabolism in Alzheimer’s but not normal brain. Neurobiol. Aging 30(4), 591–599 (2009).
   Google Scholar
• Filippov V, Song MA, Zhang K et al. Increased ceramide in brains with Alzheimer’s and other neurodegenerative diseases. J. Alzheimers Dis. 29(3), 537–547 (2012).
   Google Scholar
• Marks N, Berg MJ, Saito M. Glucosylceramide synthase decrease in frontal cortex of Alzheimer brain correlates with abnormal increase in endogenous ceramides: consequences to morphology and viability on enzyme suppression in cultured primary neurons. Brain Res. 1191, 136–147 (2008).
   Google Scholar
• Han X, Fagan AM, Cheng H, Morris JC, Xiong C, Holtzman DM. Cerebrospinal fluid sulfatide is decreased in subjects with incipient dementia. Ann. Neurol. 54(1), 115–119 (2003).
   Google Scholar
• Satoi H, Tomimoto H, Ohtani R et al. Astroglial expression of ceramide in Alzheimer’s disease brains: a role during neuronal apoptosis. Neuroscience 130(3), 657–666 (2005).
   Google Scholar
• Kosicek M, Kirsch S, Bene R et al. Nano-HPLC-MS analysis of phospholipids in cerebrospinal fluid of Alzheimer’s disease patients – a pilot study. Anal. Bioanal. Chem. 398(7–8), 2929–2937 (2010).
   Google Scholar
• Kosicek M, Zetterberg H, Andreasen N, Peter-Katalinic J, Hecimovic S. Elevated cerebrospinal fluid sphingomyelin levels in prodromal Alzheimer’s disease. Neurosci. Lett. 516(2), 302–305 (2012).
   Google Scholar
• Mattila KM, Frey H. Two-dimensional analysis of qualitative and quantitative changes in blood cell proteins in Alzheimer’s disease: search for extraneuronal markers. Appl. Theor. Electrophor. 4(4), 189–196 (1995).
   Google Scholar
• Koyama A, Okereke O, Yang T, Blacker D, Selkoe DJ, Grodstein F. Plasma Amyloid-b as a predictor of dementia and cognitive decline: a systematic review and meta-analysis. Arch. Neurol. 69(7), 824–831 (2012).
   Google Scholar
• Kalanj-Bognar S, Rundek T, Furac I, Demarin V, Cosovic C. Leukocyte lysosomal enzymes in Alzheimer’s disease and Down’s syndrome. J. Gerontol. A Biol Sci. Med. Sci. 57(1), B16–B21 (2002).
   Google Scholar
• Emiliani C, Urbanelli L, Racanicchi L et al. Up-regulation of glycohydrolases in Alzheimer’s Disease fibroblasts correlates with Ras activation. J. Biol. Chem. 278(40), 38453–38460 (2003).
   Google Scholar
• Pitto M, Raimondo F, Zoia C, Brighina L, Ferrarese C, Masserini M. Enhanced GM1 ganglioside catabolism in cultured fibroblasts from Alzheimer patients. Neurobiol. Aging 26(6), 833–838 (2005).
   Google Scholar
• Mielke MM, Bandaru VVR, Xia J et al. Serum ceramides increase the risk of Alzheimer disease: the Women’s Health and Aging Study II. Neurology 79, 633–641 (2012).
   Google Scholar
• Mielke MM, Haughey NJ, Ratnam Bandaru VV et al. Plasma ceramides are altered in mild cognitive impairment and predict cognitive decline and hippocampal volume loss. Alzheimer’s Dement. 6(5), 378–385 (2010).
   Google Scholar
• Mielke MM, Haughey NJ, Bandaru VV et al. Plasma sphingomyelins are associated with cognitive progression in Alzheimer’s disease. J. Alzheimers Dis. 27(2), 259–269 (2011).
   Google Scholar
• Han X, Rozen S, Boyle SH et al. Metabolomics in early Alzheimer’s disease: identification of altered plasma sphingolipidome using shotgun lipidomics. PLoS ONE 6(7), e21643 (2011).
   Google Scholar
• Hicks AA, Pramstaller PP, Johansson A et al. Genetic determinants of circulating sphingolipid concentrations in European populations. PLoS Genet. 5(10), e1000672 (2009). ▪ Describes the genetic variants that influence levels of circulating sphingolipids in the population.
   Google Scholar
• de la Monte SM, Longato L, Tong M, Wands JR. Insulin resistance and neurodegeneration: roles of obesity, type 2 diabetes mellitus and non-alcoholic steatohepatitis. Curr. Opin Investig. Drugs 10(10), 1049–1060 (2009). ▪ Describes potential mechanisms by which peripheral ceramides affect brain pathology.
   Google Scholar
• de la Monte SM, Tong M, Nguyen V, Setshedi M, Longato L, Wands JR. Ceramide-mediated insulin resistance and impairment of cognitive-motor functions. J. Alzheimers Dis. 21(3), 967–984 (2010).
   Google Scholar
• Ichi I, Nakahara K, Miyashita Y et al. Association of ceramides in human plasma with risk factors of atherosclerosis. Lipids 41(9), 859–863 (2006).
   Google Scholar
• Nelson JC, Jiang XC, Tabas I, Tall A, Shea S. Plasma sphingomyelin and subclinical atherosclerosis: findings from the multiethnic study of atherosclerosis. Am. J. Epidemiol. 163(10), 903–912 (2006).
   Google Scholar
• Summers SA. Ceramides in insulin resistance and lipotoxicity. Prog. Lipid Res. 45(1), 42–72 (2006).
   Google Scholar
• Holland WL, Summers SA. Sphingolipids, insulin resistance, and metabolic disease: new insights from in vivo manipulation of sphingolipid metabolism. Endocr. Rev. 29(4), 381–402 (2008).
   Google Scholar
• Haus JM, Kashyap SR, Kasumov T et al. Plasma ceramides are elevated in obese subjects with type 2 diabetes and correlate with the severity of insulin resistance. Diabetes 58(2), 337–343 (2009).
   Google Scholar
• Mielke MM, Rosenberg PB, Tschanz J et al. Vascular factors predict rate of progression in Alzheimer disease. Neurology 69(19), 1850–1858 (2007).
   Google Scholar
• Chan RB, Oliveira TG, Cortes EP et al. Comparative lipidomic analysis of mouse and human brain with Alzheimer disease. J. Biol. Chem. 287(4), 2678–2688 (2012).
   Google Scholar