About this Journal Submit a Manuscript Table of Contents
BioMed Research International
Volume 2013 (2013), Article ID 814390, 16 pages
http://dx.doi.org/10.1155/2013/814390
Review Article

The Impact of Cholesterol, DHA, and Sphingolipids on Alzheimer’s Disease

1Experimental Neurology, Saarland University, Kirrberger Street 1, 66421 Homburgr, Saar, Germany
2Neurodegeneration and Neurobiology, Saarland University, Kirrberger Street 1, 66421 Homburg, Germany
3Deutsches Institut für DemenzPrävention (DIDP), Saarland University, Kirrberger Street 1, 66421 Homburgr, Saar, Germany

Received 30 April 2013; Accepted 13 July 2013

Academic Editor: Cheng-Xin Gong

Copyright © 2013 Marcus O. W. Grimm et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. T. Dyrks, A. Weidemann, G. Multhaup et al., “Identification, transmembrane orientation and biogenesis of the amyloid A4 precursor of Alzheimer's disease,” EMBO Journal, vol. 7, no. 4, pp. 949–957, 1988. View at Scopus
  2. B. Anliker and U. Müller, “The functions of mammalian amyloid precursor protein and related amyloid precursor-like proteins,” Neurodegenerative Diseases, vol. 3, no. 4-5, pp. 239–246, 2006. View at Publisher · View at Google Scholar · View at Scopus
  3. J. Herms, B. Anliker, S. Heber et al., “Cortical dysplasia resembling human type 2 lissencephaly in mice lacking all three APP family members,” EMBO Journal, vol. 23, no. 20, pp. 4106–4115, 2004. View at Publisher · View at Google Scholar · View at Scopus
  4. F. Magara, U. Müller, Z. W. Li et al., “Genetic background changes the pattern of forebrain commissure defects in transgenic mice underexpressing the β-amyloid-precursor protein,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 8, pp. 4656–4661, 1999. View at Publisher · View at Google Scholar · View at Scopus
  5. J. P. Steinbach, U. Müller, M. Leist, Z. W. Li, P. Nicotera, and A. Aguzzi, “Hypersensitivity to seizures in β-amyloid precursor protein deficient mice,” Cell Death and Differentiation, vol. 5, no. 10, pp. 858–866, 1998. View at Scopus
  6. Tyan, S. -H, Shih et al., “Amyloid precursor protein (APP) regulates synaptic structure and function,” Molecular and Cellular Neuroscience, vol. 51, no. 1-2, pp. 43–52, 2012. View at Publisher · View at Google Scholar
  7. K. J. Lee, C. E. H. Moussa, Y. Lee et al., “Beta amyloid-independent role of amyloid precursor protein in generation and maintenance of dendritic spines,” Neuroscience, vol. 169, no. 1, pp. 344–356, 2010. View at Publisher · View at Google Scholar · View at Scopus
  8. H. S. Hoe, Z. Fu, A. Makarova et al., “The effects of amyloid precursor protein on postsynaptic composition and activity,” Journal of Biological Chemistry, vol. 284, no. 13, pp. 8495–8506, 2009. View at Publisher · View at Google Scholar · View at Scopus
  9. F. S. Esch, P. S. Keim, E. C. Beattie et al., “Cleavage of amyloid β peptide during constitutive processing of its precursor,” Science, vol. 248, no. 4959, pp. 1122–1124, 1990. View at Scopus
  10. M. P. Mattson, Z. H. Guo, and J. D. Geiger, “Secreted form of amyloid precursor protein enhances basal glucose and glutamate transport and protects against oxidative impairment of glucose and glutamate transport in synaptosomes by a cyclic GMP-mediated mechanism,” Journal of Neurochemistry, vol. 73, no. 2, pp. 532–537, 1999. View at Publisher · View at Google Scholar · View at Scopus
  11. H. Meziane, J. C. Dodart, C. Mathis et al., “Memory-enhancing effects of secreted forms of the β-amyloid precursor protein in normal and amnestic mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 21, pp. 12683–12688, 1998. View at Publisher · View at Google Scholar · View at Scopus
  12. S. Ring, S. W. Weyer, S. B. Kilian et al., “The secreted β-amyloid precursor protein ectodomain APPsα is sufficient to rescue the anatomical, behavioral, and electrophysiological abnormalities of APP-deficient mice,” Journal of Neuroscience, vol. 27, no. 29, pp. 7817–7826, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. M. Asai, C. Hattori, B. Szabó et al., “Putative function of ADAM9, ADAM10, and ADAM17 as APP α-secretase,” Biochemical and Biophysical Research Communications, vol. 301, no. 1, pp. 231–235, 2003. View at Publisher · View at Google Scholar · View at Scopus
  14. J. D. Buxbaum, K. N. Liu, Y. Luo et al., “Evidence that tumor necrosis factor α converting enzyme is involved in regulated α-secretase cleavage of the Alzheimer amyloid protein precursor,” Journal of Biological Chemistry, vol. 273, no. 43, pp. 27765–27767, 1998. View at Publisher · View at Google Scholar · View at Scopus
  15. S. Lammich, E. Kojro, R. Postina et al., “Constitutive and regulated α-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 7, pp. 3922–3927, 1999. View at Publisher · View at Google Scholar · View at Scopus
  16. R. Yan, M. J. Blenkowski, M. E. Shuck et al., “Membrane-anchored aspartyl protease with Alzheimer's disease β-secretase activity,” Nature, vol. 402, no. 6761, pp. 533–537, 1999. View at Publisher · View at Google Scholar · View at Scopus
  17. R. Vassar, B. D. Bennett, S. Babu-Khan et al., “β-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE,” Science, vol. 286, no. 5440, pp. 735–741, 1999. View at Publisher · View at Google Scholar · View at Scopus
  18. V. Y. H. Hook, T. Toneff, W. Aaron, S. Yasothornsrikul, R. Bundey, and T. Reisine, “β-amyloid peptide in regulated secretory vesicles of chromaffin cells: evidence for multiple cysteine proteolytic activities in distinct pathways for β-secretase activity in chromaffin vesicles,” Journal of Neurochemistry, vol. 81, no. 2, pp. 237–256, 2002. View at Publisher · View at Google Scholar · View at Scopus
  19. X. Hu, C. W. Hicks, W. He et al., “Bace1 modulates myelination in the central and peripheral nervous system,” Nature Neuroscience, vol. 9, no. 12, pp. 1520–1525, 2006. View at Publisher · View at Google Scholar · View at Scopus
  20. M. Willem, A. N. Garratt, B. Novak et al., “Control of peripheral nerve myelination by the β-secretase BACE1,” Science, vol. 314, no. 5799, pp. 664–666, 2006. View at Publisher · View at Google Scholar · View at Scopus
  21. W. T. Kimberly, M. J. LaVoie, B. L. Ostaszewski, W. Ye, M. S. Wolfe, and D. J. Selkoe, “γ-secretase is a membrane protein complex comprised of presenilin, nicastrin, aph-1, and pen-2,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 11, pp. 6382–6387, 2003. View at Publisher · View at Google Scholar · View at Scopus
  22. B. de Strooper, P. Saftig, K. Craessaerts et al., “Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein,” Nature, vol. 391, no. 6665, pp. 387–390, 1998. View at Publisher · View at Google Scholar · View at Scopus
  23. M. O. Grimm, I. Tomic, and T. Hartmann, “Potential external source of Aβ in biological samples,” Nature Cell Biology, vol. 4, pp. E164–E165, 2002. View at Publisher · View at Google Scholar
  24. E. Levy-Lahad, W. Wasco, P. Poorkaj et al., “Candidate gene for the chromosome 1 familial Alzheimer's disease locus,” Science, vol. 269, no. 5226, pp. 973–977, 1995. View at Scopus
  25. B. Grziwa, M. O. W. Grimm, C. L. Masters, K. Beyreuther, T. Hartmann, and S. F. Lichtenthaler, “The transmembrane domain of the amyloid precursor protein in microsomal membranes is on both sides shorter than predicted,” Journal of Biological Chemistry, vol. 278, no. 9, pp. 6803–6808, 2003. View at Publisher · View at Google Scholar · View at Scopus
  26. G. G. Glenner and C. W. Wong, “Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein,” Biochemical and Biophysical Research Communications, vol. 120, no. 3, pp. 885–890, 1984. View at Scopus
  27. J. T. Jarrett, E. P. Berger, and P. T. Lansbury Jr., “The carboxy terminus of the β amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer's disease,” Biochemistry, vol. 32, no. 18, pp. 4693–4697, 1993. View at Scopus
  28. X. Cao and T. C. Sudhof, “A Transcriptively active complex of APP with Fe65 and histone acetyltransferase Tip60,” Science, vol. 293, no. 5527, pp. 115–120, 2001. View at Publisher · View at Google Scholar
  29. S. Wang, R. Wang, L. Chen, D. A. Bennett, D. W. Dickson, and D. S. Wang, “Expression and functional profiling of neprilysin, insulin-degrading enzyme, and endothelin-converting enzyme in prospectively studied elderly and Alzheimer's brain,” Journal of Neurochemistry, vol. 115, no. 1, pp. 47–57, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. J. Y. Huang, D. M. Hafez, B. D. James, D. A. Bennett, and R. A. Marr, “Altered NEP2 expression and activity in mild cognitive impairment and Alzheimer's disease,” Journal of Alzheimer's Disease, vol. 28, no. 2, pp. 433–441, 2012. View at Publisher · View at Google Scholar · View at Scopus
  31. L. C. Walker, M. I. Diamond, K. E. Duff, and B. T. Hyman, “Mechanisms of protein seeding in neurodegenerative diseases,” JAMA Neurology, vol. 70, no. 3, pp. 304–310, 2013. View at Publisher · View at Google Scholar
  32. D. Harold, R. Abraham, P. Hollingworth et al., “Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease,” Nature Genetics, vol. 41, no. 10, pp. 1088–1093, 2009. View at Publisher · View at Google Scholar
  33. R. Ferrari, J. H. Moreno, A. T. Minhajuddin et al., “Implication of common and disease specific variants in CLU, CR1, and PICALM,” Neurobiology of Aging, vol. 33, no. 8, pp. 1846.e7–1846.e18, 2012. View at Publisher · View at Google Scholar · View at Scopus
  34. C. Reitz, G. Jun, A. Naj et al., “Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ϵ4, and the risk of late-onset Alzheimer disease in African Americans,” Journal of the American Medical Association, vol. 309, no. 14, pp. 1483–1492, 2013. View at Publisher · View at Google Scholar
  35. T. Nuutinen, T. Suuronen, A. Kauppinen, and A. Salminen, “Clusterin: a forgotten player in Alzheimer's disease,” Brain Research Reviews, vol. 61, no. 2, pp. 89–104, 2009. View at Publisher · View at Google Scholar · View at Scopus
  36. E. M. C. Schrijvers, P. J. Koudstaal, A. Hofman, and M. M. B. Breteler, “Plasma clusterin and the risk of Alzheimer disease,” Journal of the American Medical Association, vol. 305, no. 13, pp. 1322–1326, 2011. View at Publisher · View at Google Scholar · View at Scopus
  37. P. C. May, M. Lampert-Etchells, S. A. Johnson, J. Poirier, J. N. Masters, and C. E. Finch, “Dynamics of gene expression for a hippocampal glycoprotein elevated in Alzheimer's disease and in response to experimental lesions in rat,” Neuron, vol. 5, no. 6, pp. 831–839, 1990. View at Publisher · View at Google Scholar · View at Scopus
  38. G. Falgarone and G. Chiocchia, “Chapter 8: clusterin: a multifacet protein at the crossroad of inflammation and autoimmunity,” Advances in Cancer Research, vol. 104, pp. 139–170, 2009. View at Scopus
  39. H. Zhang, J. K. Kim, C. A. Edwards, Z. Xu, R. Taichman, and C. Y. Wang, “Clusterin inhibits apoptosis by interacting with activated Bax,” Nature Cell Biology, vol. 7, no. 9, pp. 909–915, 2005. View at Publisher · View at Google Scholar · View at Scopus
  40. J. J. Yerbury, S. Poon, S. Meehan et al., “The extracellular chaperone clusterin influences amyloid formation and toxicity by interacting with prefibrillar structures,” FASEB Journal, vol. 21, no. 10, pp. 2312–2322, 2007. View at Publisher · View at Google Scholar · View at Scopus
  41. W. S. Kim, M. L. Fitzgerald, K. Kang et al., “Abca7 null mice retain normal macrophage phosphatidylcholine and cholesterol efflux activity despite alterations in adipose mass and serum cholesterol levels,” Journal of Biological Chemistry, vol. 280, no. 5, pp. 3989–3995, 2005. View at Publisher · View at Google Scholar · View at Scopus
  42. Y. Ikeda, S. Abe-Dohmae, Y. Munehira et al., “Posttranscriptional regulation of human ABCA7 and its function for the apoA-I-dependent lipid release,” Biochemical and Biophysical Research Communications, vol. 311, no. 2, pp. 313–318, 2003. View at Publisher · View at Google Scholar · View at Scopus
  43. S. L. Chan, W. S. Kim, J. B. Kwok et al., “ATP-binding cassette transporter A7 regulates processing of amyloid precursor protein in vitro,” Journal of Neurochemistry, vol. 106, no. 2, pp. 793–804, 2008. View at Publisher · View at Google Scholar · View at Scopus
  44. M. Kivipelto, E. L. Helkala, M. P. Laakso et al., “Apolipoprotein E ε4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer disease,” Annals of Internal Medicine, vol. 137, no. 3, pp. 149–155, 2002. View at Scopus
  45. M. A. Pappolla, T. K. Bryant-Thomas, D. Herbert et al., “Mild hypercholesterolemia is an early risk factor for the development of Alzheimer amyloid pathology,” Neurology, vol. 61, no. 2, pp. 199–205, 2003. View at Scopus
  46. A. Solomon, M. Kivipelto, B. Wolozin, J. Zhou, and R. A. Whitmer, “Midlife serum cholesterol and increased risk of Alzheimer's and vascular dementia three decades later,” Dementia and Geriatric Cognitive Disorders, vol. 28, no. 1, pp. 75–80, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. D. Lütjohann, A. Papassotiropoulos, I. Björkhem et al., “Plasma 24S-hydroxycholesterol (cerebrosterol) is increased in Alzheimer and vascular demented patients,” Journal of Lipid Research, vol. 41, no. 2, pp. 195–198, 2000. View at Scopus
  48. J. Y. Hur, H. Welander, H. Behbahani et al., “Active γ-secretase is localized to detergent-resistant membranes in human brain,” FEBS Journal, vol. 275, no. 6, pp. 1174–1187, 2008. View at Publisher · View at Google Scholar · View at Scopus
  49. J. M. Cordy, I. Hussain, C. Dingwall, N. M. Hooper, and A. J. Turner, “Exclusively targeting β-secretase to lipid rafts by GPI-anchor addition up-regulates β-site processing of the amyloid precursor protein,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 20, pp. 11735–11740, 2003. View at Publisher · View at Google Scholar · View at Scopus
  50. E. Kojro, G. Gimpl, S. Lammich, W. März, and F. Fahrenholz, “Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the α-secretase ADAM 10,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 10, pp. 5815–5820, 2001. View at Publisher · View at Google Scholar · View at Scopus
  51. A. J. Beel, M. Sakakura, P. J. Barrett, and C. R. Sanders, “Direct binding of cholesterol to the amyloid precursor protein: an important interaction in lipid-Alzheimer's disease relationships?” Biochimica et Biophysica Acta, vol. 1801, no. 8, pp. 975–982, 2010. View at Publisher · View at Google Scholar · View at Scopus
  52. P. J. Barrett, Y. Song, W. D. van Horn et al., “The amyloid precursor protein has a flexible transmembrane domain and binds cholesterol,” Science, vol. 336, no. 6085, pp. 1168–1171, 2012. View at Publisher · View at Google Scholar
  53. M. O. W. Grimm, H. S. Grimm, I. Tomic, K. Beyreuther, T. Hartmann, and C. Bergmann, “Independent inhibition of Alzheimer disease β- and γ-secretase cleavage by lowered cholesterol levels,” Journal of Biological Chemistry, vol. 283, no. 17, pp. 11302–11311, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. P. Osenkowski, W. Ye, R. Wang, M. S. Wolfe, and D. J. Selkoe, “Direct and potent regulation of γ-secretase by its lipid microenvironment,” Journal of Biological Chemistry, vol. 283, no. 33, pp. 22529–22540, 2008. View at Publisher · View at Google Scholar · View at Scopus
  55. L. Kalvodova, N. Kahya, P. Schwille et al., “Lipids as modulators of proteolytic activity of BACE: involvement of cholesterol, glycosphingolipids, and anionic phospholipids in vitro,” Journal of Biological Chemistry, vol. 280, no. 44, pp. 36815–36823, 2005. View at Publisher · View at Google Scholar · View at Scopus
  56. A. Hosaka, W. Araki, A. Oda, Y. Tomidokoro, and A. Tamaoka, “Statins reduce amyloid β-peptide production by modulating amyloid precursor protein maturation and phosphorylation through a cholesterol-independent mechanism in cultured neurons,” Neurochemical Research, vol. 38, no. 3, pp. 589–600, 2013. View at Publisher · View at Google Scholar
  57. E. Winkler, F. Kamp, J. Scheuring, A. Ebke, A. Fukumori, and H. Steiner, “Generation of Alzheimer disease-associated amyloid beta42/43 peptide by gamma-secretase can be inhibited directly by modulation of membrane thickness,” Journal of Biological Chemistry, vol. 287, no. 25, pp. 21326–21334, 2012. View at Publisher · View at Google Scholar
  58. C. Haass, M. G. Schlossmacher, A. Y. Hung et al., “Amyloid β-peptide is produced by cultured cells during normal metabolism,” Nature, vol. 359, no. 6393, pp. 322–325, 1992. View at Publisher · View at Google Scholar · View at Scopus
  59. K. N. Dahlgren, A. M. Manelli, W. Blaine Stine Jr., L. K. Baker, G. A. Krafft, and M. J. Ladu, “Oligomeric and fibrillar species of amyloid-β peptides differentially affect neuronal viability,” Journal of Biological Chemistry, vol. 277, no. 35, pp. 32046–32053, 2002. View at Publisher · View at Google Scholar · View at Scopus
  60. A. Schneider, W. Schulz-Schaeffer, T. Hartmann, J. B. Schulz, and M. Simons, “Cholesterol depletion reduces aggregation of amyloid-beta peptide in hippocampal neurons,” Neurobiology of Disease, vol. 23, no. 3, pp. 573–577, 2006. View at Publisher · View at Google Scholar · View at Scopus
  61. X. Zhou and J. Xu, “Free cholesterol induces higher beta-sheet content in Abeta peptide oligomers by aromatic interaction with Phe19,” PLoS ONE, vol. 7, no. 9, Article ID e46245, 2012. View at Publisher · View at Google Scholar
  62. A. Y. Abramov, M. Ionov, E. Pavlov, and M. R. Duchen, “Membrane cholesterol content plays a key role in the neurotoxicity of β-amyloid: implications for Alzheimer's disease,” Aging Cell, vol. 10, no. 4, pp. 595–603, 2011. View at Publisher · View at Google Scholar · View at Scopus
  63. P. Ferrera, O. Mercado-Gómez, M. Silva-Aguilar, M. Valverde, and C. Arias, “Cholesterol potentiates β-amyloid-induced toxicity in human neuroblastoma cells: involvement of oxidative stress,” Neurochemical Research, vol. 33, no. 8, pp. 1509–1517, 2008. View at Publisher · View at Google Scholar · View at Scopus
  64. I. Sponne, A. Fifre, V. Koziel, T. Oster, J. L. Olivier, and T. Pillot, “Membrane cholesterol interferes with neuronal apoptosis induced by soluble oligomers but not fibrils of amyloid-beta peptide,” The FASEB Journal, vol. 18, no. 7, pp. 836–838, 2004. View at Scopus
  65. N. Arispe and M. Doh, “Plasma membrane cholesterol controls the cytotoxicity of Alzheimer's disease AβP (1-40) and (1-42) peptides,” FASEB Journal, vol. 16, no. 12, pp. 1526–1536, 2002. View at Publisher · View at Google Scholar · View at Scopus
  66. M. O. W. Grimm, H. S. Grimm, A. J. Pätzold et al., “Regulation of cholesterol and sphingomyelin metabolism by amyloid-β and presenilin,” Nature Cell Biology, vol. 7, no. 11, pp. 1118–1123, 2005. View at Publisher · View at Google Scholar · View at Scopus
  67. E. Canepa, R. Borghi, J. Via et al., “Cholesterol and amyloid-β: evidence for a cross-talk between astrocytes and neuronal cells,” Journal of Alzheimer's Disease, vol. 25, no. 4, pp. 645–653, 2011. View at Publisher · View at Google Scholar · View at Scopus
  68. M. O. W. Grimm, J. A. Tschäpe, H. S. Grimm, E. G. Zinser, and T. Hartmann, “Altered membrane fluidity and lipid raft composition in presenilin-deficient cells,” Acta Neurologica Scandinavica, vol. 114, no. 185, pp. 27–32, 2006. View at Publisher · View at Google Scholar · View at Scopus
  69. T. Umeda, H. Mori, H. Zheng, and T. Tomiyama, “Regulation of cholesterol efflux by amyloid β secretion,” Journal of Neuroscience Research, vol. 88, no. 9, pp. 1985–1994, 2010. View at Publisher · View at Google Scholar · View at Scopus
  70. T. J. L. van de Parre, P. J. D. F. Guns, P. Fransen et al., “Attenuated atherogenesis in apolipoprotein E-deficient mice lacking amyloid precursor protein,” Atherosclerosis, vol. 216, no. 1, pp. 54–58, 2011. View at Publisher · View at Google Scholar · View at Scopus
  71. A. Nunes, S. N. R. Pressey, J. D. Cooper, and S. Soriano, “Loss of amyloid precursor protein in a mouse model of Niemann-Pick type C disease exacerbates its phenotype and disrupts tau homeostasis,” Neurobiology of Disease, vol. 42, no. 3, pp. 349–359, 2011. View at Publisher · View at Google Scholar · View at Scopus
  72. Q. Liu, C. V. Zerbinatti, J. Zhang et al., “Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1,” Neuron, vol. 56, no. 1, pp. 66–78, 2007. View at Publisher · View at Google Scholar · View at Scopus
  73. M. Hashimoto, H. M. Shahdat, S. Yamashita et al., “Docosahexaenoic acid disrupts in vitro amyloid β1-40 fibrillation and concomitantly inhibits amyloid levels in cerebral cortex of Alzheimer's disease model rats,” Journal of Neurochemistry, vol. 107, no. 6, pp. 1634–1646, 2008. View at Publisher · View at Google Scholar · View at Scopus
  74. M. O. W. Grimm, J. Kuchenbecker, S. Grosgen et al., “Docosahexaenoic acid reduces amyloid β production via multiple pleiotropic mechanisms,” Journal of Biological Chemistry, vol. 286, no. 16, pp. 14028–14039, 2011. View at Publisher · View at Google Scholar · View at Scopus
  75. Y. Zhao, F. Calon, C. Julien et al., “Docosahexaenoic acid-derived neuroprotectin D1 induces neuronal survival via secretase- and PPARγ-mediated mechanisms in Alzheimer's disease models,” PLoS ONE, vol. 6, no. 1, Article ID e15816, 2011. View at Publisher · View at Google Scholar · View at Scopus
  76. W. J. Lukiw, J. G. Cui, V. L. Marcheselli et al., “A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease,” Journal of Clinical Investigation, vol. 115, no. 10, pp. 2774–2783, 2005. View at Publisher · View at Google Scholar · View at Scopus
  77. E. Hjorth, M. Zhu, V. C. Toro et al., “Omega-3 Fatty Acids Enhance Phagocytosis of Alzheimer's Disease-Related Amyloid-beta42 by Human Microglia and Decrease Inflammatory Markers,” Journal of Alzheimer's Disease, vol. 35, no. 4, pp. 697–713, 2013. View at Publisher · View at Google Scholar
  78. V. F. Labrousse, A. Nadjar, C. Joffre et al., “Short-term long chain omega3 diet protects from neuroinflammatory processes and memory impairment in aged mice,” PLoS One, vol. 7, no. 5, Article ID e36861, 2012. View at Publisher · View at Google Scholar
  79. Q. L. Ma, B. Teter, O. J. Ubeda et al., “Omega-3 fatty acid docosahexaenoic acid increases SorLA/LR11, a sorting protein with reduced expression in sporadic Alzheimer's disease (AD): relevance to AD prevention,” Journal of Neuroscience, vol. 27, no. 52, pp. 14299–14307, 2007. View at Publisher · View at Google Scholar · View at Scopus
  80. D. L. Sparks, S. W. Scheff, J. C. Hunsaker III, H. Liu, T. Landers, and D. R. Gross, “Induction of Alzheimer-like β-amyloid immunoreactivity in the brains of rabbits with dietary cholesterol,” Experimental Neurology, vol. 126, no. 1, pp. 88–94, 1994. View at Publisher · View at Google Scholar · View at Scopus
  81. F. S. Shie, L. W. Jin, D. G. Cook, J. B. Leverenz, and R. C. LeBoeuf, “Diet-induced hypercholesterolemia enhances brain Aβ accumulation in transgenic mice,” NeuroReport, vol. 13, no. 4, pp. 455–459, 2002. View at Scopus
  82. L. M. Refolo, B. Malester, J. LaFrancois et al., “Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model,” Neurobiology of Disease, vol. 7, no. 4, pp. 321–331, 2000. View at Publisher · View at Google Scholar
  83. L. M. Refolo, M. A. Pappolla, J. LaFrancois et al., “A cholesterol-lowering drug reduces β-amyloid pathology in a transgenic mouse model of Alzheimer's disease,” Neurobiology of Disease, vol. 8, no. 5, pp. 890–899, 2001. View at Publisher · View at Google Scholar · View at Scopus
  84. T. Kurata, K. Miyazaki, M. Kozuki et al., “Atorvastatin and pitavastatin reduce senile plaques and inflammatory responses in a mouse model of Alzheimer's disease,” Journal of Neurology Research, vol. 34, no. 6, pp. 601–610, 2012. View at Publisher · View at Google Scholar
  85. N. Sato, M. Shinohara, H. Rakugi, and R. Morishita, “Dual effects of statins on Aβ metabolism: upregulation of the degradation of APP-CTF and Aβ clearance,” Neurodegenerative Diseases, vol. 10, no. 1–4, pp. 305–308, 2012. View at Publisher · View at Google Scholar · View at Scopus
  86. K. Fassbender, M. Simons, C. Bergmann et al., “Simvastatin strongly reduces levels of Alzheimer's disease β-amyloid peptides Aβ42 and Aβ40 in vitro and in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 10, pp. 5856–5861, 2001. View at Publisher · View at Google Scholar · View at Scopus
  87. L. Cibickova, H. Radomir, M. Stanislav et al., “The influence of simvastatin, atorvastatin and high-cholesterol diet on acetylcholinesterase activity, amyloid beta and cholesterol synthesis in rat brain,” Steroids, vol. 74, no. 1, pp. 13–19, 2009. View at Publisher · View at Google Scholar · View at Scopus
  88. I. H. Park, E. M. Hwang, H. S. Hong et al., “Lovastatin enhances Aβ production and senile plaque deposition in female Tg2576 mice,” Neurobiology of Aging, vol. 24, no. 5, pp. 637–643, 2003. View at Publisher · View at Google Scholar · View at Scopus
  89. M. D. M. Haag, A. Hofman, P. J. Koudstaal, B. H. C. Stricker, and M. M. B. Breteler, “Statins are associated with a reduced risk of Alzheimer disease regardless of lipophilicity. The Rotterdam Study,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 80, no. 1, pp. 13–17, 2009. View at Publisher · View at Google Scholar · View at Scopus
  90. B. Wolozin, W. Kellman, P. Ruosseau, G. G. Celesia, and G. Siegel, “Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors,” Archives of Neurology, vol. 57, no. 10, pp. 1439–1443, 2000. View at Scopus
  91. B. Wolozin, S. W. Wang, N. C. Li, A. Lee, T. A. Lee, and L. E. Kazis, “Simvastatin is associated with a reduced incidence of dementia and Parkinson's disease,” BMC Medicine, vol. 5, article 20, 2007. View at Publisher · View at Google Scholar · View at Scopus
  92. T. D. Rea, J. C. Breitner, B. M. Psaty et al., “Statin use and the risk of incident dementia: the Cardiovascular Health Study,” Archives of Neurology, vol. 62, no. 7, pp. 1047–1051, 2005. View at Publisher · View at Google Scholar · View at Scopus
  93. Z. Arvanitakis, J. A. Schneider, R. S. Wilson et al., “Statins, incident Alzheimer disease, change in cognitive function, and neuropathology,” Neurology, vol. 70, no. 19, pp. 1795–1802, 2008. View at Publisher · View at Google Scholar · View at Scopus
  94. H. H. Feldman, R. S. Doody, M. Kivipelto et al., “Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe,” Neurology, vol. 74, no. 12, pp. 956–964, 2010. View at Publisher · View at Google Scholar · View at Scopus
  95. M. Sano, K. L. Bell, D. Galasko et al., “A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease,” Neurology, vol. 77, no. 6, pp. 556–563, 2011. View at Publisher · View at Google Scholar · View at Scopus
  96. R. J. Pawlosky, J. R. Hibbeln, J. A. Novotny, and N. Salem Jr., “Physiological compartmental analysis of α-linolenic acid metabolism in adult humans,” Journal of Lipid Research, vol. 42, no. 8, pp. 1257–1265, 2001. View at Scopus
  97. S. R. Wassall and W. Stillwell, “Polyunsaturated fatty acid-cholesterol interactions: domain formation in membranes,” Biochimica et Biophysica Acta, vol. 1788, no. 1, pp. 24–32, 2009. View at Publisher · View at Google Scholar · View at Scopus
  98. S. Gamoh, M. Hashimoto, K. Sugioka et al., “Chronic administration of docosahexaenoic acid improves reference memory-related learning ability in young rats,” Neuroscience, vol. 93, no. 1, pp. 237–241, 1999. View at Publisher · View at Google Scholar · View at Scopus
  99. M. Katakura, M. Hashimoto, H. M. Shahdat et al., “Docosahexaenoic acid promotes neuronal differentiation by regulating basic helix-loop-helix transcription factors and cell cycle in neural stem cells,” Neuroscience, vol. 160, no. 3, pp. 651–660, 2009. View at Publisher · View at Google Scholar · View at Scopus
  100. L. Dagai, R. Peri-Naor, and R. Z. Birk, “Docosahexaenoic acid significantly stimulates immediate early response genes and neurite outgrowth,” Neurochemical Research, vol. 34, no. 5, pp. 867–875, 2009. View at Publisher · View at Google Scholar · View at Scopus
  101. F. Calon, G. P. Lim, F. Yang et al., “Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model,” Neuron, vol. 43, no. 5, pp. 633–645, 2004. View at Publisher · View at Google Scholar · View at Scopus
  102. M. Soderberg, C. Edlund, K. Kristensson, and G. Dallner, “Fatty acid composition of brain phospholipids in aging and in Alzheimer's disease,” Lipids, vol. 26, no. 6, pp. 421–425, 1991. View at Scopus
  103. T. J. Montine and J. D. Morrow, “Fatty acid oxidation in the pathogenesis of Alzheimer's disease,” American Journal of Pathology, vol. 166, no. 5, pp. 1283–1289, 2005. View at Scopus
  104. W. R. Markesbery, R. J. Kryscio, M. A. Lovell, and J. D. Morrow, “Lipid peroxidation is an early event in the brain in amnestic mild cognitive impairment,” Annals of Neurology, vol. 58, no. 5, pp. 730–735, 2005. View at Publisher · View at Google Scholar · View at Scopus
  105. S. Kalmijn, L. J. Launer, A. Ott, J. C. M. Witteman, A. Hofman, and M. M. B. Breteler, “Dietary fat intake and the risk of incident dementia in the Rotterdam study,” Annals of Neurology, vol. 42, no. 5, pp. 776–782, 1997. View at Publisher · View at Google Scholar · View at Scopus
  106. M. J. Engelhart, M. I. Geerlings, A. Ruitenberg et al., “Diet and risk of dementia: does fat matter? The Rotterdam study,” Neurology, vol. 59, no. 12, pp. 1915–1921, 2002. View at Scopus
  107. P. Barberger-Gateau, L. Letenneur, V. Deschamps, K. Pérès, J. F. Dartigues, and S. Renaud, “Fish, meat, and risk of dementia: cohort study,” British Medical Journal, vol. 325, no. 7370, pp. 932–933, 2002. View at Scopus
  108. M. C. Morris, D. A. Evans, J. L. Bienias et al., “Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease,” Archives of Neurology, vol. 60, no. 7, pp. 940–946, 2003. View at Publisher · View at Google Scholar · View at Scopus
  109. E. J. Schaefer, V. Bongard, A. S. Beiser et al., “Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and alzheimer disease: the framingham heart study,” Archives of Neurology, vol. 63, no. 11, pp. 1545–1550, 2006. View at Publisher · View at Google Scholar · View at Scopus
  110. L. J. Whalley, I. J. Deary, J. M. Starr et al., “n-3 Fatty acid erythrocyte membrane content, APOE ε4, and cognitive variation: an observational follow-up study in late adulthood,” American Journal of Clinical Nutrition, vol. 87, no. 2, pp. 449–454, 2008. View at Scopus
  111. S. Oddo, A. Caccamo, J. D. Shepherd et al., “Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Aβ and synaptic dysfunction,” Neuron, vol. 39, no. 3, pp. 409–421, 2003. View at Publisher · View at Google Scholar · View at Scopus
  112. K. N. Green, H. Martinez-Coria, H. Khashwji et al., “Dietary docosahexaenoic acid and docosapentaenoic acid ameliorate amyloid-β and tau pathology via a mechanism involving presenilin 1 levels,” Journal of Neuroscience, vol. 27, no. 16, pp. 4385–4395, 2007. View at Publisher · View at Google Scholar · View at Scopus
  113. G. P. Lim, F. Calon, T. Morihara et al., “A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model,” Journal of Neuroscience, vol. 25, no. 12, pp. 3032–3040, 2005. View at Publisher · View at Google Scholar · View at Scopus
  114. M. Hashimoto, S. Hossain, T. Shimada, and O. Shido, “Docosahexaenoic acid-induced protective effect against impaired learning in amyloid β-infused rats is associated with increased synaptosomal membrane fluidity,” Clinical and Experimental Pharmacology and Physiology, vol. 33, no. 10, pp. 934–939, 2006. View at Publisher · View at Google Scholar · View at Scopus
  115. P. K. Mukherjee, V. L. Marcheselli, C. N. Serhan, and N. G. Bazan, “Neuroprotectin D1: a docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 22, pp. 8491–8496, 2004. View at Publisher · View at Google Scholar · View at Scopus
  116. Y. Freund-Levi, M. Eriksdotter-Jönhagen, T. Cederholm et al., “ω-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: omegAD study—a randomized double-blind trial,” Archives of Neurology, vol. 63, no. 10, pp. 1402–1408, 2006. View at Publisher · View at Google Scholar · View at Scopus
  117. S. Kotani, E. Sakaguchi, S. Warashina et al., “Dietary supplementation of arachidonic and docosahexaenoic acids improves cognitive dysfunction,” Neuroscience Research, vol. 56, no. 2, pp. 159–164, 2006. View at Publisher · View at Google Scholar · View at Scopus
  118. C. C. Chiu, K. P. Su, T. C. Cheng et al., “The effects of omega-3 fatty acids monotherapy in Alzheimer's disease and mild cognitive impairment: a preliminary randomized double-blind placebo-controlled study,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 32, no. 6, pp. 1538–1544, 2008. View at Publisher · View at Google Scholar · View at Scopus
  119. P. Scheltens, P. J. G. H. Kamphuis, F. R. J. Verhey et al., “Efficacy of a medical food in mild Alzheimer's disease: a randomized, controlled trial,” Alzheimer's and Dementia, vol. 6, no. 1, pp. 1–10, 2010. View at Publisher · View at Google Scholar · View at Scopus
  120. P. Scheltens, J. W. Twisk, R. Blesa et al., “Efficacy of Souvenaid in mild Alzheimer's disease: results from a randomized, controlled trial,” Journal of Alzheimer's Disease, vol. 31, no. 1, pp. 225–236, 2012. View at Publisher · View at Google Scholar
  121. P. Scheltens, “Alzheimer's and Parkinson's diseases: mechanisms, clinical strategies, and promising treatments of neurodegenerative diseases,” in Proceedings of the 11th International Conference AD/PD, Karger, Florence, Italy, 2013.
  122. M. O. W. Grimm, S. Grsgen, T. L. Rothhaar et al., “Intracellular APP domain regulates serine-palmitoyl-CoA transferase expression and is affected in alzheimer's disease,” International Journal of Alzheimer's Disease, vol. 2011, Article ID 695413, 8 pages, 2011. View at Publisher · View at Google Scholar · View at Scopus
  123. J. Tarasiuk, K. Kapica-Topczewska, A. Kulakowska et al., “Increased concentration of the CSF Tau protein and its phosphorylated form in the late juvenile metachromatic leukodystrophy form: a case report,” Journal of Neural Transmission, vol. 119, no. 7, pp. 759–762, 2012. View at Publisher · View at Google Scholar
  124. S. Keilani, Y. Lun, A. C. Stevens et al., “Lysosomal dysfunction in a mouse model of sandhoff disease leads to accumulation of ganglioside-bound amyloid-β peptide,” Journal of Neuroscience, vol. 32, no. 15, pp. 5223–5236, 2012. View at Publisher · View at Google Scholar · View at Scopus
  125. X. Han, D. M. Holtzman, D. W. McKeel Jr., J. Kelley, and J. C. Morris, “Substantial sulfatide deficiency and ceramide elevation in very early Alzheimer's disease: potential role in disease pathogenesis,” Journal of Neurochemistry, vol. 82, no. 4, pp. 809–818, 2002. View at Publisher · View at Google Scholar · View at Scopus
  126. T. Taki, “An approach to glycobiology from glycolipidomics: ganglioside molecular scanning in the brains of patients with Alzheimer's disease by TLC-blot/matrix assisted laser desorption/ionization-time of flight MS,” Biological & Pharmaceutical Bulletin, vol. 35, no. 10, pp. 1642–1647, 2012.
  127. Z. Pernber, K. Blennow, N. Bogdanovic, J. E. Mansson, and M. Blomqvist, “Altered distribution of the gangliosides GM1 and GM2 in Alzheimer's disease,” Dementia and Geriatric Cognitive Disorders, vol. 33, no. 2-3, pp. 174–188, 2012. View at Publisher · View at Google Scholar
  128. V. Filippov, M. A. Song, K. Zhang et al., “Increased ceramide in brains with alzheimer's and other neurodegenerative diseases,” Journal of Alzheimer's Disease, vol. 29, no. 3, pp. 537–547, 2012. View at Publisher · View at Google Scholar · View at Scopus
  129. L. Hejazi, J. W. H. Wong, D. Cheng et al., “Mass and relative elution time profiling: two-dimensional analysis of sphingolipids in Alzheimer's disease brains,” Biochemical Journal, vol. 438, no. 1, pp. 165–175, 2011. View at Publisher · View at Google Scholar · View at Scopus
  130. V. Martín, N. Fabelo, G. Santpere et al., “Lipid alterations in lipid rafts from Alzheimer's disease human brain cortex,” Journal of Alzheimer's Disease, vol. 19, no. 2, pp. 489–502, 2010. View at Publisher · View at Google Scholar · View at Scopus
  131. X. He, Y. Huang, B. Li, C. X. Gong, and E. H. Schuchman, “Deregulation of sphingolipid metabolism in Alzheimer's disease,” Neurobiology of Aging, vol. 31, no. 3, pp. 398–408, 2010. View at Publisher · View at Google Scholar · View at Scopus
  132. R. G. Cutler, J. Kelly, K. Storie et al., “Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 7, pp. 2070–2075, 2004. View at Publisher · View at Google Scholar · View at Scopus
  133. P. Katsel, C. Li, and V. Haroutunian, “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?” Neurochemical Research, vol. 32, no. 4-5, pp. 845–856, 2007. View at Publisher · View at Google Scholar · View at Scopus
  134. M. M. Mielke, V. V. R. Bandaru, N. J. Haughey et al., “Serum ceramides increase the risk of Alzheimer disease: the Women's Health and Aging Study II,” Neurology, vol. 79, no. 7, pp. 633–641, 2012. View at Publisher · View at Google Scholar
  135. L. Barrier, S. Ingrand, B. Fauconneau, and G. Page, “Gender-dependent accumulation of ceramides in the cerebral cortex of the APPSL/PS1Ki mouse model of Alzheimer's disease,” Neurobiology of Aging, vol. 31, no. 11, pp. 1843–1853, 2010. View at Publisher · View at Google Scholar · View at Scopus
  136. L. Barrier, B. Fauconneau, A. Nol, and S. Ingrand, “Ceramide and related-sphingolipid levels are not altered in disease-associated brain regions of APPSL and APPSL/PS1APPM146L mouse models of Alzheimer's disease: relationship with the lack of neurodegeneration?” International Journal of Alzheimer's Disease, vol. 2011, Article ID 920958, 10 pages, 2011. View at Publisher · View at Google Scholar · View at Scopus
  137. G. Dawson, R. Goswami, J. Kilkus, D. Wiesner, and S. Dawson, “The formation of ceramide from sphingomyelin is associated with cellular apoptosis,” Acta Biochimica Polonica, vol. 45, no. 2, pp. 287–297, 1998. View at Scopus
  138. R. E. Toman, V. Movsesyan, S. K. Murthy, S. Milstien, S. Spiegel, and A. I. Faden, “Ceramide-induced cell death in primary neuronal cultures: upregulation of ceramide levels during neuronal apoptosis,” Journal of Neuroscience Research, vol. 68, no. 3, pp. 323–330, 2002. View at Publisher · View at Google Scholar · View at Scopus
  139. X. Zhang, J. Wu, Y. Dou et al., “Asiatic acid protects primary neurons against C2-ceramide-induced apoptosis,” European Journal of Pharmacology, vol. 679, no. 1–3, pp. 51–59, 2012. View at Publisher · View at Google Scholar · View at Scopus
  140. J. T. Lee, J. Xu, J. M. Lee et al., “Amyloid-β peptide induces oligodendrocyte death by activating the neutral sphingomyelinase-ceramide pathway,” Journal of Cell Biology, vol. 164, no. 1, pp. 123–131, 2004. View at Publisher · View at Google Scholar · View at Scopus
  141. E. G. Zinser, T. Hartmann, and M. O. W. Grimm, “Amyloid beta-protein and lipid metabolism,” Biochimica et Biophysica Acta, vol. 1768, no. 8, pp. 1991–2001, 2007. View at Publisher · View at Google Scholar · View at Scopus
  142. G. Wang, M. Dinkins, Q. He et al., “Astrocytes secrete exosomes enriched with proapoptotic ceramide and prostate apoptosis response 4 (PAR-4): potential mechanism of apoptosis induction in Alzheimer disease (AD),” Journal of Biological Chemistry, vol. 287, no. 25, pp. 21384–21395, 2012. View at Publisher · View at Google Scholar
  143. K. Trajkovic, C. Hsu, S. Chiantia et al., “Ceramide triggers budding of exosome vesicles into multivesicular endosomes,” Science, vol. 319, no. 5867, pp. 1244–1247, 2008. View at Publisher · View at Google Scholar · View at Scopus
  144. L. Puglielli, B. C. Ellis, A. J. Saunders, and D. M. Kovacs, “Ceramide stabilizes β-site amyloid precursor protein-cleaving enzyme 1 and promotes amyloid β-peptide biogenesis,” Journal of Biological Chemistry, vol. 278, no. 22, pp. 19777–19783, 2003. View at Publisher · View at Google Scholar · View at Scopus
  145. H. K. Mi and L. Puglielli, “Two Endoplasmic Reticulum (ER)/ER golgi intermediate compartment-based lysine acetyltransferases post-translationally regulate BACE1 levels,” Journal of Biological Chemistry, vol. 284, no. 4, pp. 2482–2492, 2009. View at Publisher · View at Google Scholar · View at Scopus
  146. L. C. Edsall, G. G. Pirianov, and S. Spiegel, “Involvement of sphingosine 1-phosphate in nerve growth factor-mediated neuronal survival and differentiation,” Journal of Neuroscience, vol. 17, no. 18, pp. 6952–6960, 1997. View at Scopus
  147. R. A. Rius, L. C. Edsall, and S. Spiegel, “Activation of sphingosine kinase in pheochromocytoma PC12 neuronal cells in response to trophic factors,” FEBS Letters, vol. 417, no. 2, pp. 173–176, 1997. View at Publisher · View at Google Scholar · View at Scopus
  148. N. Takasugi, T. Sasaki, K. Suzuki et al., “BACE1 activity is modulated by cell-associated sphingosine-1-phosphate,” Journal of Neuroscience, vol. 31, no. 18, pp. 6850–6857, 2011. View at Publisher · View at Google Scholar · View at Scopus
  149. O. Ben-David and A. H. Futerman, “The role of the ceramide acyl chain length in neurodegeneration: involvement of ceramide synthases,” NeuroMolecular Medicine, vol. 12, no. 4, pp. 341–350, 2010. View at Publisher · View at Google Scholar · View at Scopus
  150. V. V. R. Bandaru, J. Troncoso, D. Wheeler et al., “ApoE4 disrupts sterol and sphingolipid metabolism in Alzheimer's but not normal brain,” Neurobiology of Aging, vol. 30, no. 4, pp. 591–599, 2009. View at Publisher · View at Google Scholar · View at Scopus
  151. J. W. Pettegrew, K. Panchalingam, R. L. Hamilton, and R. J. Mcclure, “Brain membrane phospholipid alterations in Alzheimer's disease,” Neurochemical Research, vol. 26, no. 7, pp. 771–782, 2001. View at Publisher · View at Google Scholar · View at Scopus
  152. M. Kosicek, H. Zetterberg, N. Andreasen, J. Peter-Katalinic, and S. Hecimovic, “Elevated cerebrospinal fluid sphingomyelin levels in prodromal Alzheimer's disease,” Neuroscience Letters, vol. 516, no. 2, pp. 302–305, 2012. View at Publisher · View at Google Scholar · View at Scopus
  153. M. M. Mielke, N. J. Haughey, V. V. R. Bandaru et al., “Plasma sphingomyelins are associated with cognitive progression in alzheimer's disease,” Journal of Alzheimer's Disease, vol. 27, no. 2, pp. 259–269, 2011. View at Publisher · View at Google Scholar · View at Scopus
  154. K. A. Sheikh, J. Sun, Y. Liu et al., “Mice lacking complex gangliosides develop Wallerian degeneration and myelination defects,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 13, pp. 7532–7537, 1999. View at Publisher · View at Google Scholar · View at Scopus
  155. T. Yamashita, R. Wada, T. Sasaki et al., “A vital role for glycosphingolipid synthesis during development and differentiation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 16, pp. 9142–9147, 1999. View at Publisher · View at Google Scholar · View at Scopus
  156. S. Lahiri and A. H. Futerman, “The metabolism and function of sphingolipids and glycosphingolipids,” Cellular and Molecular Life Sciences, vol. 64, no. 17, pp. 2270–2284, 2007. View at Publisher · View at Google Scholar · View at Scopus
  157. K. Simons and E. Ikonen, “Functional rafts in cell membranes,” Nature, vol. 387, no. 6633, pp. 569–572, 1997. View at Publisher · View at Google Scholar · View at Scopus
  158. I. Kracun, H. Rosner, V. Drnovsek, M. Heffer-Lauc, C. Cosovic, and G. Lauc, “Human brain gangliosides in development, aging and disease,” International Journal of Developmental Biology, vol. 35, no. 3, pp. 289–295, 1991. View at Scopus
  159. R. B. Chan, T. G. Oliveira, E. P. Cortes et al., “Comparative lipidomic analysis of mouse and human brain with Alzheimer disease,” Journal of Biological Chemistry, vol. 287, no. 4, pp. 2678–2688, 2012. View at Publisher · View at Google Scholar · View at Scopus
  160. C. G. Gottfries, I. Karlsson, and L. Svennerholm, “Membrane components separate early-onset Alzheimer's disease from senile dementia of the Alzheimer type,” International Psychogeriatrics, vol. 8, no. 3, pp. 365–372, 1996. View at Publisher · View at Google Scholar · View at Scopus
  161. M. Molander-Melin, K. Blennow, N. Bogdanovic, B. Dellheden, J. E. Månsson, and P. Fredman, “Structural membrane alterations in Alzheimer brains found to be associated with regional disease development; increased density of gangliosides GM1 and GM2 and loss of cholesterol in detergent-resistant membrane domains,” Journal of Neurochemistry, vol. 92, no. 1, pp. 171–182, 2005. View at Publisher · View at Google Scholar · View at Scopus
  162. L. Barrier, S. Ingrand, M. Damjanac, A. Rioux Bilan, J. Hugon, and G. Page, “Genotype-related changes of ganglioside composition in brain regions of transgenic mouse models of Alzheimer's disease,” Neurobiology of Aging, vol. 28, no. 12, pp. 1863–1872, 2007. View at Publisher · View at Google Scholar · View at Scopus
  163. M. O. W. Grimm, E. G. Zinser, S. Grösgen et al., “Amyloid precursor protein (app) mediated regulation of ganglioside homeostasis linking alzheimer's disease pathology with ganglioside metabolism,” PLoS ONE, vol. 7, no. 3, Article ID e34095, 2012. View at Publisher · View at Google Scholar · View at Scopus
  164. Q. Zha, Y. Ruan, T. Hartmann, K. Beyreuther, and D. Zhang, “GM1 ganglioside regulates the proteolysis of amyloid precursor protein,” Molecular Psychiatry, vol. 9, no. 10, pp. 946–952, 2004. View at Publisher · View at Google Scholar · View at Scopus
  165. O. Holmes, S. Paturi, W. Ye, M. S. Wolfe, and D. J. Selkoe, “Effects of membrane lipids on the activity and processivity of purified γ-secretase,” Biochemistry, vol. 51, no. 17, pp. 3565–3575, 2012. View at Publisher · View at Google Scholar · View at Scopus
  166. I. Peters, U. Igbavboa, T. Schütt et al., “The interaction of beta-amyloid protein with cellular membranes stimulates its own production,” Biochimica et Biophysica Acta, vol. 1788, no. 5, pp. 964–972, 2009. View at Publisher · View at Google Scholar · View at Scopus
  167. I. Y. Tamboli, K. Prager, E. Barth, M. Heneka, K. Sandhoff, and J. Walter, “Inhibition of glycosphingolipid biosynthesis reduces secretion of the β-amyloid precursor protein and amyloid β-peptide,” Journal of Biological Chemistry, vol. 280, no. 30, pp. 28110–28117, 2005. View at Publisher · View at Google Scholar · View at Scopus
  168. K. Yanagisawa, A. Odaka, N. Suzuki, and Y. Ihara, “GM1 ganglioside-bound amyloid β-protein (Aβ): a possible form of preamyloid in Alzheimer's disease,” Nature Medicine, vol. 1, no. 10, pp. 1062–1066, 1995. View at Scopus
  169. A. Kakio, S. I. Nishimoto, K. Yanagisawa, Y. Kozutsumi, and K. Matsuzaki, “Interactions of amyloid β-protein with various gangliosides in raft-like membranes: importance of GM1 ganglioside-bound form as an endogenous seed for Alzheimer amyloid,” Biochemistry, vol. 41, no. 23, pp. 7385–7390, 2002. View at Publisher · View at Google Scholar · View at Scopus
  170. M. Utsumi, Y. Yamaguchi, H. Sasakawa, N. Yamamoto, K. Yanagisawa, and K. Kato, “Up-and-down topological mode of amyloid β-peptide lying on hydrophilic/hydrophobic interface of ganglioside clusters,” Glycoconjugate Journal, vol. 26, no. 8, pp. 999–1006, 2009. View at Publisher · View at Google Scholar · View at Scopus
  171. R. Mahfoud, N. Garmy, M. Maresca, N. Yahi, A. Puigserver, and J. Fantini, “Identification of a common sphingolipid-binding domain in Alzheimer, prion, and HIV-1 proteins,” Journal of Biological Chemistry, vol. 277, no. 13, pp. 11292–11296, 2002. View at Publisher · View at Google Scholar · View at Scopus
  172. M. Wakabayashi, T. Okada, Y. Kozutsumi, and K. Matsuzaki, “GM1 ganglioside-mediated accumulation of amyloid β-protein on cell membranes,” Biochemical and Biophysical Research Communications, vol. 328, no. 4, pp. 1019–1023, 2005. View at Publisher · View at Google Scholar · View at Scopus
  173. J. A. Lemkul and D. R. Bevan, “Lipid composition influences the release of Alzheimer's amyloid β-peptide from membranes,” Protein Science, vol. 20, no. 9, pp. 1530–1545, 2011. View at Publisher · View at Google Scholar · View at Scopus
  174. T. Okada, M. Wakabayashi, K. Ikeda, and K. Matsuzaki, “Formation of toxic fibrils of Alzheimer's amyloid β-protein-(1-40) by monosialoganglioside GM1, a neuronal membrane component,” Journal of Molecular Biology, vol. 371, no. 2, pp. 481–489, 2007. View at Publisher · View at Google Scholar · View at Scopus
  175. H. Hayashi, N. Kimura, H. Yamaguchi et al., “A seed for Alzheimer amyloid in the brain,” Journal of Neuroscience, vol. 24, no. 20, pp. 4894–4902, 2004. View at Publisher · View at Google Scholar · View at Scopus
  176. N. Yamamoto, T. Matsubara, T. Sato, and K. Yanagisawa, “Age-dependent high-density clustering of GM1 ganglioside at presynaptic neuritic terminals promotes amyloid β-protein fibrillogenesis,” Biochimica et Biophysica Acta, vol. 1778, no. 12, pp. 2717–2726, 2008. View at Publisher · View at Google Scholar · View at Scopus
  177. A. Probst, D. Langui, S. Ipsen, N. Robakis, and J. Ulrich, “Deposition of β/A4 protein along neuronal plasma membranes in diffuse senile plaques,” Acta Neuropathologica, vol. 83, no. 1, pp. 21–29, 1991. View at Publisher · View at Google Scholar · View at Scopus
  178. O. Bugiani, G. Giaccone, L. Verga et al., “Alzheimer patients and Down patients: abnormal presynaptic terminals are related to cerebral preamyloid deposits,” Neuroscience Letters, vol. 119, no. 1, pp. 56–59, 1990. View at Publisher · View at Google Scholar · View at Scopus
  179. M. Eckhardt, “The role and metabolism of sulfatide in the nervous system,” Molecular Neurobiology, vol. 37, no. 2-3, pp. 93–103, 2008. View at Publisher · View at Google Scholar · View at Scopus
  180. S. Mitew, M. T. K. Kirkcaldie, G. M. Halliday, C. E. Shepherd, J. C. Vickers, and T. C. Dickson, “Focal demyelination in Alzheimer's disease and transgenic mouse models,” Acta Neuropathologica, vol. 119, no. 5, pp. 567–577, 2010. View at Publisher · View at Google Scholar · View at Scopus
  181. X. Han, H. Cheng, J. D. Fryer, A. M. Fagan, and D. M. Holtzman, “Novel role for apolipoprotein E in the central nervous system: modulation of sulfatide content,” Journal of Biological Chemistry, vol. 278, no. 10, pp. 8043–8051, 2003. View at Publisher · View at Google Scholar · View at Scopus
  182. H. Cheng, Y. Zhou, D. M. Holtzman, and X. Han, “Apolipoprotein E mediates sulfatide depletion in animal models of Alzheimer's disease,” Neurobiology of Aging, vol. 31, no. 7, pp. 1188–1196, 2010. View at Publisher · View at Google Scholar · View at Scopus
  183. Y. Zeng and X. Han, “Sulfatides facilitate apolipoprotein E-mediated amyloid-β peptide clearance through an endocytotic pathway,” Journal of Neurochemistry, vol. 106, no. 3, pp. 1275–1286, 2008. View at Publisher · View at Google Scholar · View at Scopus
  184. I. Grundke-Iqbal, K. Iqbal, and Y. C. Tung, “Abnormal phosphorylation of the microtubule-associated protein τ (tau) in Alzheimer cytoskeletal pathology,” Proceedings of the National Academy of Sciences of the United States of America, vol. 83, no. 13, pp. 44913–4917, 1986. View at Scopus
  185. I. Grundke-Iqbal, K. Iqbal, and M. Quinlan, “Microtubule-associated protein tau. A component of Alzheimer paired helical filaments,” Journal of Biological Chemistry, vol. 261, no. 13, pp. 6084–6089, 1986. View at Scopus
  186. V. M. Y. Lee, B. J. Balin, L. Otvos Jr., and J. Q. Trojanowski, “A68: a major subunit of paired helical filaments and derivatized forms of normal tau,” Science, vol. 251, no. 4994, pp. 675–678, 1991. View at Scopus
  187. M. D. Weingarten, A. H. Lockwood, S. Y. Hwo, and M. W. Kirschner, “A protein factor essential for microtubule assembly,” Proceedings of the National Academy of Sciences of the United States of America, vol. 72, no. 5, pp. 1858–1862, 1975. View at Scopus
  188. M. L. Billingsley and R. L. Kincaid, “Regulated phosphorylation and dephosphorylation of tau protein: effects on microtubule interaction, intracellular trafficking and neurodegeneration,” Biochemical Journal, vol. 323, part 3, pp. 577–591, 1997. View at Scopus
  189. A. D. C. Alonso, T. Zaidi, M. Novak, I. Grundke-Iqbal, and K. Iqbal, “Hyperphosphorylation induces self-assembly of τ into tangles of paired helical filaments/straight filaments,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 12, pp. 6923–6928, 2001. View at Publisher · View at Google Scholar · View at Scopus
  190. A. Del C. Alonso, I. Grundke-Iqbal, and K. Iqbal, “Alzheimer's disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules,” Nature Medicine, vol. 2, no. 7, pp. 783–787, 1996. View at Publisher · View at Google Scholar · View at Scopus
  191. A. D. C. Alonso, T. Zaidi, I. Grundke-Iqbal, and K. Iqbal, “Role of abnormally phosphorylated tau in the breakdown of microtubules in Alzheimer disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 12, pp. 5562–5566, 1994. View at Publisher · View at Google Scholar · View at Scopus
  192. T. Kawarabayashi, M. Shoji, L. H. Younkin et al., “Dimeric amyloid β protein rapidly accumulates in lipid rafts followed by apolipoprotein E and phosphorylated tau accumulation in the Tg2576 mouse model of Alzheimer's disease,” Journal of Neuroscience, vol. 24, no. 15, pp. 3801–3809, 2004. View at Publisher · View at Google Scholar · View at Scopus
  193. P. Hernandez, G. Lee, M. Sjoberg, and R. B. MacCioni, “Tau phosphorylation by cdk5 and Fyn in response to amyloid peptide Aβ25-35: involvement of lipid rafts,” Journal of Alzheimer's Disease, vol. 16, no. 1, pp. 149–156, 2009. View at Publisher · View at Google Scholar · View at Scopus
  194. R. Distl, S. Treiber-Held, F. Albert, V. Meske, K. Harzer, and T. G. Ohm, “Cholesterol storage and tau pathology in Niemann-Pick type C disease in the brain,” Journal of Pathology, vol. 200, no. 1, pp. 104–111, 2003. View at Publisher · View at Google Scholar · View at Scopus
  195. S. Love, L. R. Bridges, and C. P. Case, “Neurofibrillary tangles in Niemann-Pick disease type C,” Brain, vol. 118, part 1, pp. 119–129, 1995. View at Scopus
  196. R. Distl, V. Meske, and T. G. Ohm, “Tangle-bearing neurons contain more free cholesterol than adjacent tangle-free neurons,” Acta Neuropathologica, vol. 101, no. 6, pp. 547–554, 2001. View at Scopus
  197. N. Mattsson, H. Zetterberg, S. Bianconi et al., “γ-Secretase-dependent amyloid-β is increased in Niemann-Pick type C: a cross-sectional study,” Neurology, vol. 76, no. 4, pp. 366–372, 2011. View at Publisher · View at Google Scholar · View at Scopus
  198. N. Sawamura, J. S. Gong, W. S. Garver et al., “Site-specific Phosphorylation of Tau Accompanied by Activation of Mitogen-activated Protein Kinase (MAPK) in Brains of Niemann-Pick Type C Mice,” Journal of Biological Chemistry, vol. 276, no. 13, pp. 10314–10319, 2001. View at Publisher · View at Google Scholar · View at Scopus
  199. F. Glöckner, V. Meske, D. Lütjohann, and T. G. Ohm, “Dietary cholesterol and its effect on tau protein: a study in apolipoprotein e-deficient and P301L human tau mice,” Journal of Neuropathology and Experimental Neurology, vol. 70, no. 4, pp. 292–301, 2011. View at Publisher · View at Google Scholar · View at Scopus
  200. A. Rahman, S. Akterin, A. Flores-Morales et al., “High cholesterol diet induces tau hyperphosphorylation in apolipoprotein e deficient mice,” FEBS Letters, vol. 579, no. 28, pp. 6411–6416, 2005. View at Publisher · View at Google Scholar · View at Scopus
  201. N. R. Bhat and L. Thirumangalakudi, “Increased tau phosphorylation and impaired brain insulin/IGF signaling in mice fed a high fat/high cholesterol diet,” Journal of Alzheimer's Disease, 2013. View at Publisher · View at Google Scholar
  202. M. Boimel, N. Grigoriadis, A. Lourbopoulos et al., “Statins reduce the neurofibrillary tangle burden in a mouse model of tauopathy,” Journal of Neuropathology and Experimental Neurology, vol. 68, no. 3, pp. 314–325, 2009. View at Publisher · View at Google Scholar · View at Scopus
  203. R. G. Riekse, G. Li, E. C. Petrie et al., “Effect of statins on Alzheimer's disease biomarkers in cerebrospinal fluid,” Journal of Alzheimer's Disease, vol. 10, no. 4, pp. 399–406, 2006. View at Scopus
  204. A. M. Nicholson and A. Ferreira, “Increased membrane cholesterol might render mature hippocampal neurons more susceptible to β-Amyloid-induced calpain activation and tau toxicity,” Journal of Neuroscience, vol. 29, no. 14, pp. 4640–4651, 2009. View at Publisher · View at Google Scholar · View at Scopus
  205. S. Y. Park and A. Ferreira, “The generation of a 17 kDa neurotoxic fragment: an alternative mechanism by which tau mediates β-amyloid-induced neurodegeneration,” Journal of Neuroscience, vol. 25, no. 22, pp. 5365–5375, 2005. View at Publisher · View at Google Scholar · View at Scopus
  206. A. Ferreira and E. H. Bigio, “Calpain-mediated tau cleavage: a mechanism leading to neurodegeneration shared by multiple tauopathies,” Molecular Medicine, vol. 17, no. 7-8, pp. 676–685, 2011. View at Publisher · View at Google Scholar · View at Scopus
  207. C. Thornton, N. J. Bright, M. Sastre, P. J. Muckett, and D. Carling, “AMP-activated protein kinase (AMPK) is a tau kinase, activated in response to amyloid β-peptide exposure,” Biochemical Journal, vol. 434, no. 3, pp. 503–512, 2011. View at Publisher · View at Google Scholar · View at Scopus
  208. Z. Cai, L. J. Yan, K. Li, S. H. Quazi, and B. Zhao, “Roles of AMP-activated protein kinase in Alzheimer's disease,” NeuroMolecular Medicine, vol. 14, no. 1, pp. 1–14, 2012. View at Publisher · View at Google Scholar · View at Scopus
  209. V. Vingtdeux, P. Davies, D. W. Dickson, and P. Marambaud, “AMPK is abnormally activated in tangle-and pre-tangle-bearing neurons in Alzheimer's disease and other tauopathies,” Acta Neuropathologica, vol. 121, no. 3, pp. 337–349, 2011. View at Publisher · View at Google Scholar · View at Scopus
  210. C. H. Reynolds, J. C. Betts, W. P. Blackstock, A. R. Nebreda, and B. H. Anderton, “Phosphorylation sites on tau identified by nanoelectrospray mass spectrometry: differences in vitro between the mitogen-activated protein kinases ERK2, c-Jun N-terminal kinase and P38, and glycogen synthase kinase-3β,” Journal of Neurochemistry, vol. 74, no. 4, pp. 1587–1595, 2000. View at Publisher · View at Google Scholar · View at Scopus
  211. S. J. Greco, S. Sarkar, J. M. Johnston, and N. Tezapsidis, “Leptin regulates tau phosphorylation and amyloid through AMPK in neuronal cells,” Biochemical and Biophysical Research Communications, vol. 380, no. 1, pp. 98–104, 2009. View at Publisher · View at Google Scholar · View at Scopus
  212. Q. L. Ma, F. Yang, E. R. Rosario et al., “β-Amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: suppression by omega-3 fatty acids and curcumin,” Journal of Neuroscience, vol. 29, no. 28, pp. 9078–9089, 2009. View at Publisher · View at Google Scholar · View at Scopus
  213. C. Julien, C. Tremblay, A. Phivilay et al., “High-fat diet aggravates amyloid-beta and tau pathologies in the 3xTg-AD mouse model,” Neurobiology of Aging, vol. 31, no. 9, pp. 1516–1531, 2010. View at Publisher · View at Google Scholar · View at Scopus
  214. G. P. Gellermann, T. R. Appel, P. Davies, and S. Diekmann, “Paired helical filaments contain small amounts of cholesterol, phosphatidylcholine and sphingolipids,” Biological Chemistry, vol. 387, no. 9, pp. 1267–1274, 2006. View at Publisher · View at Google Scholar · View at Scopus
  215. I. Tooyama, T. Yamada, S. U. Kim, and P. L. McGeer, “Immunohistochemical study of A2B5-positive ganglioside in postmortem human brain tissue of Alzheimer disease, amyotrophic lateral sclerosis, progessive supranuclear palsy and control cases,” Neuroscience Letters, vol. 136, no. 1, pp. 91–94, 1992. View at Publisher · View at Google Scholar · View at Scopus
  216. H. Geekiyanage, A. Upadhye, and C. Chan, “Inhibition of serine palmitoyltransferase reduces Abeta and tau hyperphosphorylation in a murine model: a safe therapeutic strategy for Alzheimer's disease,” Neurobiol Aging, vol. 34, no. 8, pp. 2037–2051, 2013. View at Publisher · View at Google Scholar
  217. H. Q. Xie and G. V. W. Johnson, “Ceramide selectively decreases tau levels in differentiated PC12 cells through modulation of calpain I,” Journal of Neurochemistry, vol. 69, no. 3, pp. 1020–1030, 1997. View at Scopus